Dr. Robin Carhart-Harris: The Science of Psychedelics for Mental Health | Huberman Lab Podcast

Introduction

In this section, Andrew Huberman introduces the podcast and his guest, Dr. Robin Carhart-Harris. He provides an overview of the topics that will be discussed in the podcast.

Introducing Dr. Robin Carhart-Harris

• Dr. Robin Carhart-Harris is a distinguished professor of Neurology and Psychiatry at the University of California San Francisco.

• He is one of the leading researchers in the field of psychedelics and how they change neural circuitry in the brain.

• His laboratory is responsible for understanding how psilocybin, LSD, and DMT change neural circuitry in the brain such that new ideas and new forms of learning occur.

• The discussion will cover both clinical trials and why treatments with psychedelics work or do not work to treat major depression.

Understanding Psychedelics

• The discussion will cover how psychedelics are being applied to expand different aspects of human mind including creativity intelligence and much more.

• Dr. Carhart Harris teaches us about the history of studying psychedelics as well as how legislature surrounding psychedelics are evolving in United States and elsewhere for use in treating psychiatric challenges.

Long-term Effects of Psychedelics

• The discussion covers long-term effects of psychedelics on rewiring the brain.

Sponsorship Message: Eight Sleep

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The Importance of Blood Glucose Levels

In this section, the speaker discusses the importance of blood glucose levels and how they impact energy levels and overall health.

Blood Glucose Levels and Food Impact

• Blood glucose or blood sugar levels are important for assessing how different foods and activities impact energy levels.

• Certain foods can cause spikes in blood glucose levels, leading to post-eating dips in energy levels.

• Removing these foods and substituting them with others can even out energy levels.

Benefits of Ketone IQ

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Increasing Blood Ketones

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Live Events in September 2023

In this section, the speaker announces two live events happening in September 2023.

Live Events Details

• Two live events will take place in Toronto on September 12th and Chicago on September 28th.

• Both events will include a lecture and question-and-answer period entitled "The Brain Body Contract" discussing tools related to mental health, physical health, and performance.

• To attend either event, go to hubermanlab.com/tour and use the code "huberman" for early access to tickets.

Discussion with Dr. Robin Carhart-Harris

In this section, the speaker interviews Dr. Robin Carhart-Harris about his work pioneering the use of psychedelics for treating clinical conditions.

Psychedelics and Their Effects

• Dr. Robin Carhart-Harris is a researcher who has been pioneering the use of psychedelics for treating specific clinical conditions.

• Psychedelics are drugs that mimic aspects of psychosis in their action but have signature psychological effects that go beyond just mimicking psychotic symptoms.

• The name "psychedelic" was coined by Humphrey Osmond, a Brit excommunicated living in Canada, who felt dissatisfied with these compounds being under the category of psychotomimetics.

• The etymology of psychedelic comes from Osmond's search for a more apt term to speak to the principal component of their action.

• Psychedelics potentially reveal insights into how the brain works and can be used clinically to treat certain conditions.

Etymology and Pharmacology of Psychedelics

In this section, the speaker discusses the origin of the term "psychedelic" and its meaning. They also talk about how psychedelics work on a particular receptor in the brain.

Origin of the Term "Psychedelic"

• Psyche means human mind or soul in ancient Greek.

• The other component means to make clear or visible.

• Psychedelics reveal aspects of the psyche that are not ordinarily visible.

Pharmacology of Psychedelics

• Classic psychedelics work on a particular receptor in the brain, serotonin 2A receptor.

• The speaker believes that while pharmacology is useful, we cannot neglect subjective experience.

Revealing Aspects of the Mind

In this section, the speaker talks about how psychedelics can reveal aspects of the mind that are not obvious otherwise.

Blind Sight Phenomenon

• Blind sight refers to non-conscious processing below conscious awareness but still influencing perception.

• It's different from revealing aspects of the psyche through psychedelics.

Unconscious Processing

• Psychologists talk about unconscious processing in psychoanalysis and psychodynamic psychology.

• Personal unconscious includes repressed memories such as traumatic memories and difficult relationships.

Psychedelics and Conscious Awareness

In this section, the speaker discusses how psychedelics can bring up repressed material that has therapeutic value. They also talk about the importance of classic psychedelics in catalyzing the therapeutic process.

The Action of Psychedelics

• Psychoanalysis used dreaming as a way to access the unconscious, but now we know that psychedelics can bring up repressed material.

• Classic psychedelics like LSD and psilocybin reveal personal or transpersonal insights that catalyze the therapeutic process with strong emotional release.

• Without the action of classic psychedelics, we wouldn't be as interested in psychedelics today.

Clinical Trials with Psilocybin

• The speaker discusses clinical trials involving psilocybin as a principal hallucinatory psychedelic agent found in magic mushrooms.

• Dosages used in these trials are typically 25 milligrams of psilocybin, compared to more frequent use of very small amounts (one milligram over three weeks).

• One gram of magic mushrooms contains an average of how many milligrams of psilocybin? This is important for understanding microdosing versus macro dosing.

Microdosing vs. Macro Dosing

• A microdose is a sub-perceptible dose of a classic psychedelic like LSD or psilocybin that has no noticeable altered state effects.

• Typically, one day on and one day off or one day on and two days off is the protocol for microdosing.

Lack of Compelling Evidence for Microdosing

In this section, the speaker discusses the lack of compelling evidence for microdosing due to weak study designs and practical limitations.

Challenges in Studying Microdosing

• There is a lack of compelling evidence for microdosing due to weak study designs.

• It is difficult to conduct studies on microdosing because it requires permission to give people a micro dose that they can take home with them.

• A course of micro dosing might require participants to be in the lab three times a week for X number of weeks, which is hard to do in a lab study.

Study Design Challenges

• Conducting studies on microdosing is expensive and requires suitable controls such as placebo control.

• A study conducted in New Zealand has some interesting preliminary data but hasn't been published yet.

• Positive findings have been presented around improvements in mood, but it's too early to get excited about that.

Citizen Science Study on LSD Microdosing

In this section, the speaker talks about a citizen science study on LSD microdosing and its results.

Creative Study Design

• The speaker was involved in a creative study design with colleagues at Imperial College London led by Balázs Szigeti.

• Participants were instructed to do their own blinding and placebo-controlled blinding of their own micro dosing.

• The study used LSD tabs chopped up into gel capsules opaque with other empty capsules as placebos.

• Barcode scan technique was used so that participants could break the code later on but once shuffled up they no longer knew which ones had the micro dose or not.

Results and Controversy

• The majority of the effect was from thinking that you got a micro dose, which was a victory for the power of the placebo response.

• The results created controversy as people did not want to believe it.

• The study was a first mover kind of science and fascinating.

Psilocybin Clinical Trial for Depression

In this section, the speaker discusses psilocybin clinical trials for depression and compares 25 milligrams of psilocybin to 10 milligrams of psilocybin and Lexapro.

Dosage Comparison

• The speaker was involved in a clinical trial comparing 25 milligrams of psilocybin to 10 milligrams of psilocybin and Lexapro.

• It is unclear if 25 milligrams of psilocybin would be perceptible or cause hallucinations.

Treatment Results

• Psilocybin has shown promise in treating depression in clinical trials.

• The treatment involves one or two doses with therapy sessions before and after the treatment.

• Participants have reported significant improvements in mood and quality of life.

Psilocybin Trials and Experience

In this section, the speaker discusses the percentage of psilocybin in magic mushrooms and the typical dosage used in clinical trials. They also talk about the importance of the psychedelic experience during therapy sessions.

Psilocybin Dosage and Percentage

• The percentage of psilocybin in mushroom mass is around 1%.

• One gram of magic mushrooms contains approximately 10 milligrams of psilocybin.

• Clinical trials typically use dosages ranging from 10 to 25 milligrams.

Importance of Psychedelic Experience

• Certain kinds of experiences rated with subjective rating scales predict therapeutic outcomes strongly and reliably.

• During a psilocybin therapy session, patients typically experience initial anxiety followed by noticing patterns, colors, and dynamic organic qualities in their mind's eye.

• Patients wear an eye mask during therapy sessions to create settled conditions. Music is played throughout the session, starting with spacious music that builds into atmospheric music.

Components of a Typical Therapy Session

This section provides an overview of what happens during a typical psilocybin therapy session.

Participants

• Two mental health professionals are present during a therapy session, ideally one psychiatrist or clinical psychologist and one other kind of psychotherapist or psychiatric nurse.

• An individual who has ingested the drug participates in the session.

Music

• Music is played throughout the session, starting with spacious music that builds into atmospheric music.

• There might be some tribal drums in the distance or something as it develops.

Setting

• The therapy session takes place in a settled environment.

• Patients wear an eye mask during therapy sessions to create settled conditions.

Consistency

• There is very little variability between different sites that have done this work on these conditions.

The Role of Music in Psychedelic Therapy

In this section, the speaker discusses the role of music in psychedelic therapy and how it has not been tested properly. He shares his hypothesis that there is a positive interaction between music and psychedelics.

Music as a Staple Component

• All published studies on psychedelic therapy have music as a staple component.

• There is a positive interaction between music and psychedelics that needs to be tested better.

Combination Treatment

• Psychedelic therapy is a combination treatment with music.

• There is a synergy between psychedelics and music.

Athletic Greens Sponsorship

In this section, the speaker talks about Athletic Greens, which is sponsoring the podcast. He explains why he takes Athletic Greens and what it contains.

Benefits of Athletic Greens

• Athletic Greens covers all foundational nutritional needs.

• It contains probiotics for gut health.

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Taste and Convenience

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Letting Go in Psychedelic Therapy

In this section, the speaker discusses the importance of "letting go" in psychedelic therapy. He talks about how patients need to allow themselves to experience the full effects of psychedelics without trying to constrain their sensory or cognitive experience.

Allowing the Experience

• Patients need to allow themselves to experience the full effects of psychedelics.

• "Letting go" is critical for patients in psychedelic therapy.

Unconscious and Letting Go

• Psychedelics reveal something that's there all the time but that we don't have access to.

• The importance of "letting go" in biological terms is not yet fully understood.

Encouraging Trust, Letting Go, and Being Open

In this section, the speaker discusses the importance of trust, letting go, and being open in psychedelic therapy. The speaker explains how these components are measured and how they predict therapeutic outcomes.

The Components of Trust, Letting Go, and Being Open

• Trust is about establishing a therapeutic rapport with patients. It is measured using a visual analog scale item on the morning of dosing and predicts the quality of the experience under the drug.

• Letting go refers to a readiness to surrender and not resist. It is also measured and predicts response.

• Being open involves confronting difficult emotions or experiences with curiosity rather than resistance. This can be challenging for vulnerable populations but is crucial for positive outcomes.

The Phases of Psychedelic Therapy

• A student working on a PhD project characterizes different phases of psychedelic experiences. The early phase is dominated by negative emotions such as anxiety and struggle.

• The latter half tends to be more positive with breakthroughs or feelings of calmness. There may be a threading through of concepts related to earlier traumas or self-discovery.

This transcript excerpt focuses on encouraging trust, letting go, and being open in psychedelic therapy. The speaker emphasizes that these components are crucial for positive outcomes in treating depression with psychedelics.

Fears Associated with Psychedelic Use

In this section, the speaker discusses the common fears associated with taking psychedelics and how they relate to the nature of the mind.

Common Fears

• People often fear losing their minds or going insane when taking psychedelics.

• Even if someone knows about psychedelics, they may still fear that they will go mad or die.

• These fears are dose-dependent and stem from the way these drugs affect the mind.

Increased Communication in the Brain Under Psychedelic Influence

In this section, the speaker discusses recent findings on increased communication between brain areas under psychedelic influence and its potential therapeutic benefits.

Enhanced Communication Between Brain Areas

• Under psychedelic influence, there is an increase in global functional connectivity or communication between different brain areas.

• This effect transcends modules and becomes much more intermodular, crossing different modalities.

• The activation of serotonin 2A receptors is thought to be responsible for this increased communication.

Therapeutic Benefits

• Recent findings suggest that some or all of this enhanced communication may be maintained after a psychedelic journey is over.

• This increased communication could play a role in the incredible positive therapeutic outcomes seen with psychedelic-assisted therapy.

Psychedelics and Increased Connectivity

In this section, the speaker discusses the possibility of increased connectivity in the brain due to activation of serotonin 2A receptors by psychedelics. The speaker questions whether this increased connectivity is responsible for the subjective experience or if it is a distinct phenomenon layered on top of some other effect of psychedelic drugs.

Increased Connectivity and Subjective Experience

• Activation of serotonin 2A receptor leads to increased connectivity in the brain.

• It is unclear whether increased connectivity causes subjective experiences or if they happen in parallel.

• Causality between increased connectivity and subjective experience is circular, with both influencing each other.

Developing Non-Hallucinogenic Psychedelic Drugs

• There is a movement within the scientific community that studies psychedelics to develop drugs that can cure or alleviate symptoms of depression or trauma without producing hallucinations.

• Laboratories are modifying psychedelics so that they have potential therapeutic application for treating depression but zero hallucinogenic properties.

• The speaker expresses skepticism about this approach, as it seems illogical and difficult to fit together. They also question whether removing the subjective experience from psychedelic therapy would be effective.

Microdosing and Serotonin 2A Receptor Agonists

In this section, the speakers discuss microdosing and its potential therapeutic effects. They also explore the possibility of developing selective serotonin 2A receptor agonists that are not psychedelic.

Microdosing and Therapeutic Effects

• Microdosing involves taking doses below the perceptual or awareness threshold over a longer period to alter circuits without hallucinating.

• Microdosing is sub-perceptible and does not have psychedelic action because it does not reveal the psyche.

• Microdosing can drive a therapeutic response by directly stimulating serotonin receptors, but this effect can also be achieved with SSRIs.

Selective Serotonin 2A Receptor Agonists

• There are no non-psychedelic drugs that selectively agonize serotonin 2A receptors for therapeutic use in psychiatry.

• There are dopamine agonists used to treat Parkinson's disease, but they do not selectively stimulate serotonin 2A receptors.

• The lack of selective serotonin 2A receptor stimulators for therapeutic use in psychiatry is a limitation of current pharmacotherapy.

Neuroplasticity and Psychedelics

In this section, the speakers discuss neuroplasticity and how psychedelics may affect structural changes in neurons. They also explore how long these changes last after a psychedelic experience.

Neuroplasticity and Structural Changes

• Psychedelics have been shown to increase communication components between brain areas during and after drug effects wear off.

• Neuroplasticity is associated with growth of dendrites and spines, which are communication points between neurons.

• The duration of increased connectivity and structural brain changes after a psychedelic experience is not yet known.

Questions on Neuroplasticity

• It is unclear how much neuroplasticity and structural changes in neurons contribute to the observed increase in communication across systems during and after psychedelic experiences.

• The duration of increased connectivity and structural brain changes after a psychedelic experience is not yet known.

Decrease in Modularity and Increase in Global Connectivity

In this section, the speaker discusses how they measure a decrease in modularity and an increase in global connectivity. They also talk about how these changes are seen acutely and even three weeks later. The relationship between these changes and mental health outcomes is also discussed.

Changes in Brain Function

• A decrease in modularity and an increase in global connectivity are observed.

• These changes are seen acutely and even three weeks later.

• The magnitude of the change correlates with the improvement of symptom severity.

• Extreme modularity of brain function may be depressive.

Relationship to Mental Health Outcomes

• The relationship between these changes and mental health outcomes is discussed.

• The magnitude of the change correlates with the improvement of symptom severity.

Crosstalk Between Different Modules of the Brain

In this section, the speaker talks about crosstalk between different modules of the brain. They discuss how increasing crosstalk is strongly correlated with a positive therapeutic outcome for depression.

Increased Crosstalk

• Increasing crosstalk between different modules of the brain is strongly correlated with a positive therapeutic outcome for depression.

Flexible Mode of Brain Functioning

• Increasing crosstalk suggests a more flexible mode of brain functioning.

• Sharper cognition is associated with more modularity, while increased flexibility may be associated with creativity.

Linear vs Non-linear Thinking

In this section, the speaker talks about the differences between linear and non-linear thinking. They discuss how there may be therapeutic value in being able to move along the continuum from more linear to non-linear thinking.

Linear Thinking

• Linear thinking is associated with analytical, modular brain function.

• A more modular system may be associated with a more passy, analytical way of thinking.

Non-linear Thinking

• Non-linear thinking is associated with creative, globally interconnected brain function.

• Increased flexibility and divergent associations may be associated with creativity.

Psychedelic Therapy and the Brain

In this section, the speakers discuss how psychedelic therapy can help individuals with depression and anxiety by altering their perception of time. They also talk about the importance of macro doses over micro doses in psychedelic therapy.

Altering Perception of Time

• Extreme depressive and anxiety states alter perception of time.

• Cognitive bias in depression makes everything seem hopeless and that there is no light at the end of the tunnel.

• Being stuck in a rut cuts off from other sensory modalities or modules, making it difficult to connect with others.

• Decrease in modularity or an opening up of the brain could relate to an opening up of the mind that is enduring after a psychedelic dosing session.

Macro Doses vs Micro Doses

• Scientists doing work with psychedelics suggest that one or two, maybe three macro doses in a controlled safe setting are more effective than microdosing.

• Evidence for macro doses being more effective is compelling while microdosing remains appealing but not scientifically proven.

Psychedelic Therapy Sessions

• Typically, one to three sessions spaced out over one to three weeks are used for psychedelic therapy dosing sessions.

• Three sessions were used in a current anorexia trial using psilocybin therapy for anorexia. The results showed alleviation of obsessive thoughts about food, willingness to consume healthier amounts of food, and improved weight at long follow-up.

The Importance of Integration Phase

In this section, the speaker discusses the importance of the integration phase after taking psychedelics and how it can maximize neuroplasticity and brain changes in a positive way.

Integration Phase

• After taking psychedelics, it is important to reintegrate into daily life.

• The integration phase involves consolidating insights gained during the session through daily conversations with therapists or journaling.

• Maximizing on neuroplasticity and brain changes in a positive way requires understanding how long the integration phase lasts and how often one should think about insights gained.

• Integration lasts a lifetime, but therapeutic teams cannot be there for a lifetime. It becomes a practice that individuals must keep up with.

Psychedelic Therapy as a Leg Up

In this section, the speaker talks about how psychedelic therapy can give individuals a leg up in dealing with mental health issues.

Psychedelic Therapy

• Psychedelic therapy gives individuals a leg up in dealing with mental health issues by making it easier to do very difficult work such as processing trauma.

• Therapeutic teams can treat individuals to an extent, but beyond that point, it becomes an individual's responsibility to continue practicing what they have learned during psychedelic therapy sessions.

Psychedelic Therapy

In this section, the speaker discusses the benefits of psychedelic therapy over chronic pharmacotherapy. Psychedelic therapy allows individuals to sit with their experiences rather than suppress them.

Benefits of Psychedelic Therapy

• Psychedelic therapy allows individuals to sit with their experiences rather than suppress them.

• It promotes mindfulness and present-centeredness, allowing people to process and let go of negative experiences without reacting.

• Emerging data suggests that psychedelics can be effective treatments for depression and trauma by giving people access to a better version of themselves.

• The use of psychedelics in therapy is becoming more accepted and mainstream.

First-Time Use of Psychedelics Study

In this section, the speaker discusses a study on first-time use of psychedelics. The study was conducted on healthy volunteers who were middle-aged, with an average age of 40.

Study Details

• The study was conducted on healthy volunteers who were middle-aged, with an average age of 40.

• Participants received small doses of psilocybin as a placebo before receiving a larger dose (25mg).

• All staff members were female, which may have been a potential confound but did not seem to affect the results.

• Significant improvements in well-being were observed at the end of the trial.

Study Design and Results

In this section, the speaker discusses the study design and results of a repeated measures design where participants were given a placebo before being given psilocybin. The study recorded brain activity using EEG headsets and MRI scanning to look at functional connectivity and properties of brain anatomy.

Repeated Measures Design

• Participants were given a placebo before being given psilocybin.

• EEG headsets were used to record brain activity during the experience.

• MRI scanning was done before and after to look at functional connectivity and properties of brain anatomy.

Results

• Significant improvements in psychological well-being were seen with 25 milligrams of psilocybin.

• An increase in informational complexity of ongoing brain activity was observed with psilocybin use.

• Diffusion tensor imaging showed changes in major tracks between prefrontal cortex, thalamus, and striatum.

• Two prefrontal tracks changed in direction of decrease in axial diffusivity, indicating higher fidelity of communication between regions.

Anatomical Changes in Brain Connectivity

In this section, the speaker discusses anatomical changes observed in diffusion tensor imaging that looked at cabling of the brain's white matter tracks. The change was observed between prefrontal cortex, thalamus, and striatum.

Diffusion Tensor Imaging

• Diffusion tensor imaging looks at cabling of the brain's white matter tracks.

• Change was observed between prefrontal cortex, thalamus, and striatum.

Anatomical Changes

• Change was observed in major tracks between prefrontal cortex, thalamus, and striatum.

• Decrease in axial diffusivity indicated higher fidelity of communication between regions.

Brain Anatomy and Cognitive Flexibility

In this section, the speaker discusses a study on brain anatomy and cognitive flexibility. The study found that a 25mg dose of a certain drug improved cognitive flexibility in participants, but there were no correlations with changes in brain anatomy.

Study Results

• Participants showed improvement in cognitive flexibility after taking a 25mg dose of the drug.

• There were no correlations between changes in brain anatomy and psychological outcomes.

• The change in brain anatomy observed was opposite to what is seen in an aging brain or with pathology of aging.

• This is just one study, but it was conducted with immense rigor.

Psilocybin for Fibromyalgia Treatment

In this section, the speaker discusses a study on using psilocybin therapy to treat fibromyalgia syndrome. Fibromyalgia is characterized by generalized chronic pain and has been controversial in medicine due to its subjective nature.

Study Details

• Psilocybin therapy was used to treat fibromyalgia syndrome.

• There is interesting literature around how trauma can relate to issues related to inflammation and how that can express into things like fibromyalgia syndrome.

• Prior assumptions should not be made about uncovering trauma in every case.

• The team has treated eight patients so far.

Psilocybin and MDMA Therapy

In this section, the speaker discusses the differences between psilocybin and MDMA therapy. They also talk about how these therapies are used to treat different conditions.

Psilocybin Therapy

• The study involves giving one dose of psilocybin to patients with fibromyalgia.

• Most patients have not done psilocybin before, making it a first-time experience for them.

• Patients are not encouraged to focus on their pain during the session, unlike in PTSD work where patients are encouraged to focus on their trauma.

• Classic psychedelic therapy involves going inside oneself by putting on eye shades and focusing inward.

MDMA Therapy

• MDMA therapy involves more directed dialogue and empathic connection between people.

• Eye contact is a key part of human social cognitive connective networks in MDMA therapy.

• The therapeutic process in MDMA therapy is driven by suggestion, which can be seen as suggestive priming or biasing by skeptics.

• Pre-trial expectancy was measured for both conditions in the psilocybin therapy versus telepran trial.

Psychedelic Therapy and Pre-Trial Expectancy

In this section, the speaker discusses the relationship between pre-trial expectancy and response to psychedelic therapy.

Pre-Trial Expectancy and Response

• A sample bias was found where most people had higher expectations for psilocybin's efficacy versus SSRI Lexapro.

• Pre-trial expectancy for acetylopram predicted response to acetylopram across virtually every single measure of depression, anxiety, and well-being.

• High pre-trial expectancy did not predict response to psilocybin therapy, indicating that classic psychedelic therapy is not just a placebo response or an amplification of the placebo response.

• The direct therapeutic action of classic psychedelic therapy must be something else, such as residual increase in global connectivity.

Classic Psychedelics for Depression Treatment

In this section, the speaker discusses why there is a lack of attention towards LSD in depression treatment trials.

Use of LSD in Trials

• There are promising results for using classic psychedelics like psilocybin for treating depression, anorexia, and fibromyalgia.

• There is a lack of attention towards LSD in these trials due to its longer trip duration and stigma associated with it.

• The term "microdose" can be dangerously misleading since a macro dose of LSD can still be measured in micrograms.

• A study day with psilocybin lasts 4 to 6 hours while the FDA requires participants to stay in the lab until 8 hours post-dose, making it impractical for scientists to conduct LSD trials.

Long Days of Psychedelic Therapy

In this section, the guest talks about the long days involved in conducting psychedelic therapy sessions and how it can be challenging for both patients and staff.

Length of LSD and Psilocybin Sessions

• LSD sessions can last anywhere from 8 to 15 hours, depending on the dose.

• Psilocybin sessions typically last around 8 hours or more, depending on the dose.

• Patients may still feel the effects of psilocybin even after 6 p.m., which can make it difficult to close out a session.

Challenges with Staffing and Expenses

• The cost of staffing is one of the biggest expenses associated with psychedelic therapy sessions.

• There is interest in shortening the length of these sessions to reduce costs while maintaining therapeutic outcomes.

Combining Psilocybin and MDMA Therapies

In this section, the guest discusses combining psilocybin and MDMA therapies for therapeutic purposes.

The Hippie Flip

• Some people self-administer a combination of psilocybin and MDMA known as a "hippie flip."

• The use of MDMA can balance out some of the negative effects that psilocybin may have on mood during a trip.

Therapeutic Potential

• While combining compounds is not recommended without proper research, underground therapists do work with this combo.

Combining MDMA and Psilocybin for Therapy

In this section, the speaker discusses the potential benefits of combining MDMA and psilocybin in therapy. He explains that while psilocybin can help patients reach deep places related to their suffering, it can be overwhelming and aggressive. On the other hand, MDMA offers a more positive experience but may not take patients as deep. The speaker suggests that combining these two substances could offer advantages in certain cases.

Benefits of Combining MDMA and Psilocybin

• Precision medicine is a buzz term in medicine today, and combining MDMA and psilocybin could offer advantages in certain cases.

• Psilocybin can get patients to deep places related to their suffering, but it can be overwhelming and aggressive.

• MDMA offers a more directionally positive experience than psilocybin.

• Combining these two substances could offer advantages by allowing patients to go back to those deep places safely.

Limitations of Combining MDMA and Psilocybin

• While there are benefits to combining these two substances, they also have limitations.

• Classic psychedelics like psilocybin provide an honest experience that includes both heaven and hell.

• Getting right up next to trauma is the only way to deal with it effectively.

English DMT and its Effects

In this section, Tim Ferriss discusses the effects of DMT and how it is used therapeutically. He also talks about the chemistry of DMT and its impact on brain networks.

Therapeutic Use of DMT

• The Veteran Solutions initiative in Mexico uses ibogaine followed by one or two doses of DMT to help veterans deal with various issues.

• People who have undergone this therapy describe their experience with DMT as "the most profound experience of my entire life" and "like being attached to the shock wave of an atom bomb."

• These statements are significant because they come from individuals who have existed at the extremes of human experience.

Chemistry and Impact on Brain Networks

• DMT is a direct stimulator of the serotonin 2A receptor, making it a classic psychedelic.

• It is less potent than psilocybin but has a stickiness for the serotonin 2A receptor that matches its potency.

• Five methoxy DMT (5-MeO-DMT), another compound similar to DMT, is also used therapeutically.

• Both compounds are smoked or vaped, with some underground practitioners using vape pens to titrate dosage.

• 5-MeO-DMT may be more reliable for ego dissolution experiences, while DMT provides wilder effects.

Ego Dissolution

• Ego dissolution refers to the idea that we have a concept of self from an early age, which can be dissolved through psychedelics like DMT.

• Ego dissolution can lead to a loss of self-identity and immersion in everything.

Ego Dissolution and Molecular Continuity

In this section, the speakers discuss the concept of ego dissolution and molecular continuity. They explore how everything is interconnected, and how boundaries are just a construct.

The Characteristics of Ego Dissolution

• Ego dissolution is defined by boundaries.

• A major characteristic of the ego dissolution experience is feeling interconnected with other people and the world at large.

• The positive aspect of ego dissolution is realizing that there is molecular continuity in life.

• The construction of our mind creates an illusory sense of self.

Boundaries and Construct

• Everything in the brain is connected to everything else, making it one big macro module.

• Boundaries are just a construct, whether it's in family or science.

• It's a fun game to decide where to draw the line between what's me and what isn't me.

Psychedelics and Ego Dissolution

• Classic psychedelics cause serotonin 2A activation which leads to ego dissolution.

• MDMA doesn't cause ego dissolution in the same way as classic psychedelics but can soften the ego and increase empathy for others.

Ego Dissolution and Drugs

In this section, the speakers discuss the concept of ego dissolution and how drugs modulate it. They also talk about why psychedelics are more likely to cause ego dissolution than other drugs.

Ego Dissolution and Drug Modulation

• Different drugs affect the brain in different ways.

• Cocaine makes people's egos super inflated, while psychedelics cause ego dissolution.

• Psychedelics target serotonin 2A receptors, which are heavily expressed in the cortex or "recent brain."

• Psychedelics scramble up brain activity, leading to entropic action that spreads out the system and dissolves boundaries.

The Paradox of Ego Dissolution

• During a trip, the ego might go away, leading to profound insights about interconnectedness.

• However, after coming down from a trip, the ego often comes back with a vengeance.

• People with chronic depression may relapse after treatment with psychedelics.

Challenges of Psychedelic Therapy

• Despite promising results in trials, psychedelic therapy is still illegal in many places.

The Current State of Legality and Progression Towards Legality

In this section, the speaker discusses the current state of legality and progression towards legality for psychedelics. They also touch on the role of big pharma in this process.

Silos in Psychedelic Research

• The speaker identifies different silos in psychedelic research, including laboratories like Matthew Johnson's, Roland Griffiths', and Nolan Williams' that study the effects of psychedelics in human beings.

• These labs are studying clinical applications for the treatment of depression, anorexia, fibromyalgia, trauma, and MDMA.

• Therapists are accessing clean sources of MDMA, psilocybin, LSD to administer them illegally based on studies published by these labs.

• There is a recreational/open market black market where people can purchase psychedelics illegally. However, caution is advised as fentanyl lacing with fentanyl is now showing up in MDMA and psychedelics purchased on the street.

Legal Status

• Psychedelics are illegal unless used in a clinical trial. Possessing or selling them can result in criminal charges ranging from misdemeanors to felonies with years in prison.

• Clinical trials are ongoing but most people are not familiar with how different phases relate to proximity to legality.

• Psilocybin has been decriminalized in Oakland but it is not yet legal.

Progression Towards Legality

• It is unclear when psychedelics will become legal for therapeutic use outside of clinical trials.

Clinical Trials and MDMA Therapy

In this section, the speaker discusses clinical trials and the key phase to know about, which is phase three. They also talk about the work that has been done with MDMA therapy for post-traumatic stress disorder (PTSD) and how it has gone through two successful phase three trials.

Phase Three Trials

• Phase three trials are licensing trials that demonstrate whether a medicine is good enough to be licensed by regulators such as the FDA.

• The work done with MDMA therapy for PTSD has gone through two successful phase three trials.

• The results of the first trial were published and showed remarkable remission rates of around 67%.

• Some of those remission rates for trauma were years, which is different from ongoing dosing needed for psilocybin.

Rollout of MDMA Therapy

• The data from the phase three trials for MDMA therapy is being filed now, and a decision may be made this year with rollout happening as early as next year.

• MAPS would potentially become the provider of MDMA therapy because they have done the work and set themselves up to do so. However, there are questions about who can provide it and where one can get clean sources of MDMA.

• There is a big question mark on whether MAPS training can be used as training for clinicians to become providers. A mental health professional will need to provide dosing, but not necessarily a psychiatrist.

Providing Access to MDMA Therapy

In this section, the speaker talks about providing access to MDMA therapy once it becomes available.

Referral and Training

• There is a question of where the referral for MDMA therapy will come from, whether it will be from a psychiatrist or a general physician.

• MAPS training has been required for clinicians to participate in the phase three trials, but there are questions about whether this training is sufficient for clinicians to become providers.

• A licensed and certified provider who has undergone some training will need to provide MDMA therapy. There will also be stipulations on the basic underlying professionalism of the clinician who provides.

Physician Presence

• A physician must be present or within ready access in case of an emergency during MDMA therapy sessions.

Compass and Other Psychedelic Research

In this section, the speaker discusses the progress of Compass and other psychedelic research centers across the globe.

Compass Progress

• Compass is a multi-site organization with teams of labs geographically spread out.

• Trials for treatment-resistant depression have just started, with an estimated completion date of 2026.

• The work on soliciting phase three trials has only just begun for Compass.

Other Psychedelic Research Centers

• There are many psychedelic research centers across the globe, with the first one in London opening in 2019.

• These centers are exploring different indications such as anorexia, fibromyalgia syndrome, methamphetamine use disorder, Parkinson's disease, chronic lower back pain, bipolar disorder and OCD.

• Small investigator-led studies are reporting positive results in very difficult to treat disorders.

Positive Results in Psychedelic Therapy

In this section, the speaker talks about how small investigator-led studies are reporting positive results in very difficult to treat disorders.

Positive Results

• At least four trials have reported really positive results in very difficult to treat disorders.

• Philanthropy and donors are interested in supporting these sorts of studies because they or their family members suffer from psychiatric illness for which current big pharma approaches simply have not worked.

Evolution of Psychedelics

In this section, the speaker discusses how psychedelics were once viewed as poison but now being viewed as a potential therapeutic.

Evolution of Psychedelics

• Meditation and psychedelics were once close cousins in the cultural framework.

• Studies exploring how meditation can provide advantages for the mind and even for mental health have been conducted, while studies on psychedelics are now catching up.

• Psychedelics were viewed as making people crazy in the past, but now they are being viewed as a potential therapeutic.

Critique and Bad Practice in Psychedelic Therapy

In this section, the speaker talks about critique and bad practice in psychedelic therapy.

Critique and Bad Practice

• There is critique on psychedelic therapy due to boundary crossing issues that have caused some problems.

The Potential of Psychedelic Therapy

In this section, the speaker discusses the potential of psychedelic therapy and how it differs from traditional treatments.

The Need for Paradigm Shifts in Mental Health Treatment

• Gene therapy is advancing, including directed gene therapy using CRISPR.

• Current treatments for mental health have not progressed since the 1950s.

• Psychedelic therapy offers a paradigm shift in mental health treatment that could lead to significant improvements.

Understanding Psychedelic Therapy

• Psychedelic therapy is different from traditional treatments and may not be for everyone.

• There is great value in understanding what psychedelic therapy is and how it works.

• Small groups of individuals are driving the movement towards psychedelic therapy as a viable treatment option.

Gratitude and Conclusion

• The speaker expresses gratitude for those working towards improving mental health outcomes through psychedelic therapy.

• The speaker thanks the audience for their time and provides links to studies in his laboratory.

Dr. Carhart-Harris's Research and Support

In this section, Dr. Carhart-Harris discusses his research on psychedelics and provides links for those interested in supporting or participating in his studies.

Psychedelic Science Research

• Dr. Carhart-Harris discusses the science and clinical uses of psychedelics.

• Links to support Dr. Carhart-Harris's research or inquire about being a research subject are provided in the show note captions.

• Links to Dr. Carhart-Harris's Twitter account and other social media accounts are also provided in the show note captions.

• The huberman Lab podcast has partnered with Momentous Supplements, which can be found at livemomentis.com/huberman.

Supporting the Podcast

This section provides ways to support The Huberman Lab podcast.

Ways to Support

• Subscribe to the YouTube channel for free.

• Subscribe to the podcast on both Spotify and Apple, leave a five-star review, and check out the sponsors mentioned throughout the episode.

• Put questions, comments, or guest suggestions in the comments section on YouTube.

Social Media and Newsletter

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Social Media and Newsletter

• Follow Dr. Huberman on all social media platforms (Facebook, LinkedIn, Twitter, Instagram), where he posts about science-related tools.

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