Dr. Karl Deisseroth, a medical doctor and research scientist at Stanford School of Medicine, discusses his groundbreaking work using channelopsins, proteins from algae, to control the activity of neurons in the brain and body using light. This technology has the potential to revolutionize the treatment of psychiatric illnesses and disorders of movement and perception. Dr. Deisseroth emphasizes the importance of understanding and healing the mind, as well as the future of psychedelic treatments for psychiatric illness. Efforts are being made to develop blood tests for mental diseases such as depression, schizophrenia, and autism. The biggest challenges in treating mental health include the strong stigma associated with psychiatric diseases and the difficulty in accurately understanding and describing emotions and feelings. Dr. Deisseroth also discusses the potential of vagus nerve stimulation, the use of channelopsins in gene therapy to restore light sensitivity in the eyes, and the use of optogenetics to target specific brain regions. The video also covers topics such as the most effective drugs for mental illness having the most side effects, the use of dialogue with patients to guide treatment, and the use of CLARITY, a method that creates transparent brains for studying brain structure. The video concludes with discussions on the human brain's unique structures and capabilities, the potential of psychedelics and MDMA in treating mental health conditions, and Dr. Deisseroth's new book "Projections: A Story of Emotions."
Introduction
Dr. Karl Deisseroth, a medical doctor and research scientist at Stanford School of Medicine, is the first guest on the Huberman Lab Podcast. His groundbreaking work involves using channelopsins, proteins from algae, to control the activity of neurons in the brain and body using light. This technology has the potential to revolutionize the treatment of psychiatric illnesses and disorders of movement and perception. Dr. Deisseroth's book, "Projections: A Story of Human Emotions," explains how the brain functions and the discovery of these transformative technologies. The podcast episode discusses the importance of understanding and healing the mind, as well as the future of psychedelic treatments for psychiatric illness.
Using Language to Understand the Mind
Using Language to Understand the Mind
- Neurology focuses on diagnosing and treating disorders with physical manifestations, while psychiatry deals with disorders without physical markers.
- Psychiatry relies on language and rating scales to assess symptoms and make diagnoses.
- Lack of speech can be a symptom of mental disorders such as depression, schizophrenia, and autism.
- Collaboration between psychiatry and neurology is necessary in cases where both fields intersect.
- Language can be used as a tool to gain insights into the workings of the mind and develop new treatments for mental health conditions.
- Collaboration between different fields, such as neuroscience and psychiatry, is important to advance our understanding of the mind and improve patient care.
Blood Tests For Mental Disease
Efforts are being made to develop quantitative blood tests for mental diseases such as depression, schizophrenia, and autism. Currently, external EEGs are used to analyze brain waves and frequencies, but they lack accuracy and confidence for individual patients. However, since psychiatric diseases are physical and result from dysfunctional brain circuits and connections, it is believed that measurable indicators will eventually be discovered. This development would be beneficial as it would provide quick and precise measurements, reducing the time-consuming process of eliciting symptoms. However, there is a potential for abuse or misuse, which is a concern in all areas of medicine.
Key points:
- Efforts are underway to develop blood tests for mental diseases like depression, schizophrenia, and autism.
- Current methods like external EEGs lack accuracy and confidence for individual patients.
- Psychiatric diseases are physical and result from dysfunctional brain circuits and connections.
- Measurable indicators for mental diseases are expected to be discovered.
- Blood tests would provide quick and precise measurements, reducing the time-consuming process of eliciting symptoms.
- Concerns exist regarding the potential for abuse or misuse of these tests.
The Largest Challenges Facing Treatment of Mental Health
The biggest challenge facing psychiatry and the treatment of mental illness today is the strong stigma associated with psychiatric diseases. This stigma prevents patients from seeking help and leads to untreated conditions, which can worsen symptoms and even lead to additional problems. Many people feel that they should be able to handle their mental health issues on their own, but seeking professional help is often beneficial.
Key points:
- Stigma associated with psychiatric diseases prevents patients from seeking help and leads to untreated conditions
- Patients often feel they should be able to handle their mental health issues on their own
- Seeking professional help is often beneficial
Another challenge in psychiatry is the difficulty in accurately understanding and describing emotions and feelings. There is a disconnect between the clinical definitions of emotions and the colloquial use of words, which makes it challenging for psychiatrists to diagnose and treat patients effectively.
Key points:
- Difficulty in accurately understanding and describing emotions and feelings
- Disconnect between clinical definitions of emotions and colloquial use of words
- Challenging for psychiatrists to diagnose and treat patients effectively
The largest challenges facing treatment of mental health include the difficulty of understanding and accurately assessing a patient's internal experiences and emotions. Psychiatrists strive to go beyond jargon and delve into real-world examples of how patients are feeling, such as their level of hope, anticipation, and future planning. However, even with introspection and insight, psychiatrists do not have all the answers and cannot fully comprehend what is happening in a patient's mind. The dopamine system, which is involved in motivated behaviors, may play a role in anticipation and hope.
Key points:
- Difficulty of understanding and accurately assessing a patient's internal experiences and emotions
- Psychiatrists strive to go beyond jargon and delve into real-world examples of how patients are feeling
- Dopamine system may play a role in anticipation and hope
The largest challenges facing the treatment of mental health include accurately measuring and diagnosing symptoms. Physical actions such as sleep and eating patterns are important criteria for diagnosing depression, but they can vary greatly among individuals. Establishing a baseline for each person and tracking changes over time is crucial, but collecting this baseline information from healthy individuals raises ethical issues. Utilizing technology like phones and accelerometers may provide a solution for collecting baseline data.
Key points:
- Difficulty of accurately measuring and diagnosing symptoms
- Sleep and eating patterns vary greatly among individuals
- Establishing a baseline and tracking changes over time is crucial
- Ethical issues in collecting baseline information from healthy individuals
- Utilizing technology like phones and accelerometers may provide a solution for collecting baseline data
The largest challenges in treating mental health include the complexity of the brain, the lack of understanding of the underlying mechanisms, and the need for personalized treatments. Privacy concerns also pose a challenge in sharing patient data for research purposes.
Key points:
- Complexity of the brain and lack of understanding of underlying mechanisms
- Need for personalized treatments
- Privacy concerns in sharing patient data for research purposes
Predicting Depression & Suicide
Researchers are developing devices to detect early signs of depression, such as changes in voice inflection or physical movements. This technology aims to provide individuals with early warning signs so they can seek help. Psychiatrists currently rely on observations from family members or patients themselves to identify early signs of depression. Dr. Karl Deisseroth emphasizes the potential of using technology to predict depression and suicide by gathering information about a person's behavior and mental state. This can aid in providing effective care.
Drugs That Work for Brain Illness
Psychiatry has successfully treated brain illnesses through medications and talk therapy, with cognitive behavioral therapy being effective in treating panic disorder and psychiatric medications alleviating symptoms of conditions like schizophrenia. However, there is still a lack of understanding about the underlying circuits in the brain that cause mental illnesses, leading to the need for more targeted and effective treatments.
Key points:
- Cognitive behavioral therapy helps patients identify and derail panic attacks in as little as six to 12 sessions.
- Psychiatric medications, such as anti-psychotics, alleviate positive symptoms of schizophrenia like hallucinations and paranoia.
- Negative symptoms of schizophrenia, characterized by withdrawal and thought blocking, are also addressed in psychiatric treatment.
- Treatments like electroconvulsive therapy exist for treatment-resistant depression, but their mechanisms of effectiveness are not fully understood.
- Uncovering the circuits in the brain responsible for mental illnesses is the goal for developing more precise and effective treatments.
What Would A Cure For the Broken Mind Look Like?
A cure for the broken mind would involve understanding the natural biology and activity patterns of the brain, as well as identifying specific circuits responsible for mental disorders. Key points include:
- Many psychiatric treatments have been discovered by chance, highlighting the need for a comprehensive understanding of the brain.
- Observations of improvements in autistic children's symptoms during fevers suggest a potential link between fever and brain function.
- The complexity of social interaction and information processing in individuals with autism could provide valuable insights into brain regions involved in merging complex data streams.
- Studying social behavior in other animals can help gain a better understanding of the circuits involved in mental disorders.
- Understanding the cells in different brain regions and their connections can help researchers restore proper functioning by tweaking specific elements within these circuits.
Channelopsins: Tools For Understanding & Treating the Mind
Channelrhodopsins are proteins created by algae that can be activated by light, allowing charged particles to pass through cell membranes. This discovery has been instrumental in understanding animal behavior and has potential applications in the clinic.
Key points:
- Channelrhodopsins allow for the manipulation of neural activity using light.
- Optogenetics, the technique of inserting the gene for channelrhodopsins into mammalian neurons and using light to activate them, has been used to study sensation, cognition, and action.
- Optogenetics has been used in laboratory settings with various animals to understand neural activity.
- The ultimate goal is to apply optogenetics in clinical settings for therapeutic purposes.
- Challenges in optogenetics include packing a large number of channelrhodopsins into cells without damaging them and ensuring specificity in targeting certain types of cells.
- After years of development, optogenetics has become a widely used tool in studying and manipulating neural activity in animal models.
Curing Blindness with Channelopsins
Scientists have made a breakthrough in curing blindness by using channelrhodopsins to restore light sensitivity in the eyes of a blind patient with retinal degeneration. This achievement, accomplished through gene therapy after almost a decade of research, has significant implications not only for optogenetics in patients but also for understanding brain circuitry. By gaining insights into how the brain works, more precise and efficient treatments for neurological conditions can be developed.
Key points:
- Channelrhodopsins have been successfully used in gene therapy to restore light sensitivity in the eyes of a blind patient with retinal degeneration.
- This breakthrough is the result of nearly 10 years of research and development.
- The application of optogenetics in patients is remarkable, but the broader significance lies in advancing our understanding of brain circuitry.
- Understanding brain circuitry can lead to more targeted and effective treatments for various neurological conditions.
- Dr. Karl Deisseroth and Botond Roska share a vision of using technology to alleviate patient suffering.
Why Karl Became a Scientist
Karl became a scientist because of his deep interest in the brain, which started from a young age. He was fascinated by the power of words and how they could evoke emotions. Wanting to understand this, he decided to study the human brain and initially planned to become a neurosurgeon. However, during his medical school rotations, he discovered a neglect syndrome in a patient with thalamic damage, which sparked his interest in research.
- Karl's interest in the brain started from a young age due to his fascination with the power of words and emotions.
- He initially planned to become a neurosurgeon but became interested in research after discovering a neglect syndrome in a patient.
- Karl's interest in understanding and helping people with mental health issues was sparked during a rotation in psychiatry.
- His interest in poetry, particularly the works of Borges, influenced his path towards becoming a scientist.
- Karl developed methods to control neurons using light and algae proteins.
Vagus Nerve In Depression
Summary: The vagus nerve shows potential as a treatment for depression due to its accessibility and ability to send signals to the brain without invasive procedures. Vagus nerve stimulation is currently used for epilepsy and depression, but its effectiveness varies and it has side effects. Optogenetics could improve its efficacy by targeting specific cells in the vagus nerve. However, more research is needed to understand which cells and pathways are responsible for symptom relief in depression.
Challenges To Overcome for Treating Mental Illness with Channelopsins
The main challenge in treating mental illness with channelopsins is delivering the channelopsin gene into specific areas of the body and delivering light to stimulate those areas. The solution involves using adeno-associated viruses (AAVs) as gene delivery mechanisms, which can be injected into specific parts of the body. These AAVs carry the channelopsin gene and additional DNA that controls expression in specific cells, allowing for precise targeting and stimulation of areas involved in mood regulation. Other challenges include the need for brighter light to activate enough opsins and the requirement for the light to be of the right wavelength. The device used for stimulation is about half a millimeter in size and can be controlled through a phone app, similar to vagus nerve stimulation.
Using the Dialogue with Patients to Guide Treatment
Using dialogue with patients to guide treatment involves regularly checking in with patients to assess their progress and any potential side effects. This is done by asking specific questions about their experiences and adjusting the treatment plan accordingly. The goal is to ensure that patients are on a safe and effective regime.
How Our Eyes Reveal Our Mental Health
The eyes provide valuable insights into a person's mental health, revealing their arousal state and potential control knobs. However, it is important to consider other factors such as body language and verbal content. Key points include:
- Pupil dilation can indicate arousal, whether positive or negative.
- Eye contact is important for establishing connection, but can be problematic if too intense.
- Other factors like body posture and verbal content should be considered alongside eye cues.
- In psychiatry, decisions can be made based on phone calls by focusing on the data stream available, such as the tone of voice.
- Excessive blinking may be linked to lying, while lack of blinking may be linked to sociopathy.
- The lubrication of the eyes and frequency of blinking are influenced by our overall arousal state.
- Light plays a significant role in regulating our circadian biology and our desire to be awake or asleep.
Controlling Structures Deep In the Brain
Controlling Structures Deep In the Brain
- Optogenetics is a technique used to target specific brain regions and understand their role in behaviors.
- The habenula and raphe are examples of brain regions that can influence an individual's response to life's pressures.
- Current psychiatric treatments lack specificity and their mechanisms of relief are uncertain.
- Optogenetics holds promise for the future, but its effectiveness relies on a better understanding of how to utilize its specificity.
The Most Effective Drugs Often Have the Most Side Effects
The most profound aspect of the text is that some of the most effective anti-psychotic drugs, like clozapine, have the most side effects.
- Clozapine acts on various receptors, including serotonin, muscarinic, and dopamine receptors.
- Clozapine can cause changes in blood cell counts and other terrible side effects.
- Despite the side effects, taking clozapine can resolve symptoms, including auditory hallucinations in schizophrenic individuals.
- Taking clozapine can also cause physical sensations like dizziness and drooling due to off-target effects.
- Clozapine is not recommended for non-schizophrenic individuals due to the same side effects.
Do Psychiatrists Take the Drugs They Prescribe?
Psychiatrists often sample the drugs they prescribe to better understand their effects and improve treatment recommendations. However, personal experience should not solely guide clinical decisions.
Key points:
- Psychiatrists use firsthand experience to recognize the effects of different medications.
- Personal experience helps improve treatment recommendations.
- Clinical decisions should not be solely based on personal experience.
- Psychiatrists envision a future with more specific medications and fewer side effects.
- Optogenetics is a technique that provides a causal understanding of brain circuits.
- Understanding specific circuits and cells can lead to more effective medications.
- Medication development would be revolutionized by targeting specific brain circuits.
Moving From Experimental Tools To Novel Treaments
The transition from experimental tools to novel treatments for psychiatric diseases is discussed in the video. The goal is to develop drugs that can target specific cells and alleviate symptoms without invasive procedures. This transition is already happening at the individual patient level at Stanford and will continue to progress with new drugs and multi-centered clinical trials. The potential for using existing safe and approved medications for new psychiatric purposes based on causal optogenetics is also highlighted.
Brain-Machine Interfaces & Neuralink
Brain-machine interfaces (BMIs) have the potential to revolutionize the understanding and treatment of psychiatric and neurological diseases. By collecting information from thousands of neurons in the brain, BMIs offer insights into pathological activity patterns and provide opportunities for intervention. Despite being invasive and carrying risks, BMIs have already shown promise in psychiatry, particularly in deep brain stimulation for disorders like OCD. In the future, true brain-machine interfaces like Neuralink could detect and correct abnormalities in brain activity, offering targeted stimulation for more effective treatment of conditions like ADHD.
ADHD & Dr. Deissroth’s Approach To Focusing His Mind
The most profound aspect of the topic is Dr. Deisseroth's approach to focusing his mind and finding relief from ADHD symptoms through stillness and deep thinking.
- ADHD is a condition characterized by symptoms of hyperactivity or inattention.
- Treatment options, such as stimulants like Adderall, are available, but there is debate over who should be treated.
- ADHD can manifest in different ways, with some individuals being hyperactive while others are inattentive.
- Dr. Deisseroth personally finds that he needs to be still in order to think deeply, while others may have their best thoughts while running.
- Quantitative EEG-based diagnoses are being explored for ADHD.
- Lifestyle factors, such as excessive phone use, may induce subclinical or clinical-like ADHD symptoms.
- Activities involving impact, such as skateboarding and boxing, can provide relief from ADHD symptoms.
- Behaviors and interaction with technology, such as phones and email, may induce or reactivate ADHD-like symptoms.
- Social and occupational functioning is important in diagnosing psychiatric conditions.
- Checking one's phone can be adaptive in today's world, and managing interactions well is important.
How Dr. Deisseroth Balances A Career In Medicine, Science & Family
Dr. Karl Deisseroth, a clinician and scientist, manages a large laboratory while also balancing a family of five children. He organizes his day and week by focusing on the unit of the day and ensuring he has at least an hour of uninterrupted thinking time. He also carves out additional blocks of time, such as midnight to 2:00 AM, for specific tasks like writing. Dr. Deisseroth emphasizes the importance of protecting these small pockets of time and being disciplined to avoid overwhelming obligations.
- Dr. Deisseroth organizes his day and week by focusing on the unit of the day and ensuring he has uninterrupted thinking time.
- He carves out additional blocks of time, such as midnight to 2:00 AM, for specific tasks like writing.
- Dr. Deisseroth emphasizes the importance of protecting these small pockets of time and being disciplined to avoid overwhelming obligations.
New Ways of Exploring Brains: CLARITY
CLARITY is a revolutionary method developed by Dr. Karl Deisseroth that allows scientists to explore the structure of the brain without dissecting it. It involves building a gel-like substance within the cells of the brain, which acts as a scaffold. This gel can then be used to physically anchor and preserve molecules of interest, such as proteins and RNAs, while removing unwanted substances like lipids and fats. The result is a transparent brain with all the important molecules still intact at the cellular and subcellular level. This technique, known as hydrogel-tissue chemistry, has opened up new possibilities for understanding and studying the brain.
- CLARITY is a method that creates transparent brains by building a gel-like substance within brain cells.
- The gel anchors and preserves molecules of interest while removing unwanted substances.
- The result is a transparent brain with intact molecules at the cellular and subcellular level.
- This technique, known as hydrogel-tissue chemistry, allows for new possibilities in brain research.
What Is Special About the Human Brain?
The most profound aspect of the human brain is its unique structures and highly developed capabilities compared to other animals.
Key points:
- Humans are not superior in all aspects compared to other animals.
- Animals, including mice, can be studied to understand complex phenomena like dissociation.
- Dissociation, a common experience in trauma, has been studied in both mice and humans, revealing insights into its circuit basis.
- Research on ketamine and dissociative drugs in mice has provided insights into dissociation and corresponding brain activity.
- Collaboration with the Stanford Comprehensive Epilepsy Center has shown similar brain activity patterns in a human patient experiencing dissociation.
- Optogenetics allows researchers to manipulate brain activity and observe the effects on behavior and perception.
- By activating specific groups of neurons, dissociative states and visual sensations have been induced in mice.
- Optogenetics provides a way to causally link brain activity to behavior and perception, enhancing our understanding of the human brain.
- Research on animal brains, particularly mice, has been crucial for understanding and treating human diseases.
Psychedelics
Psychedelic medicine, such as LSD and psilocybin, has the potential to effectively treat depression and trauma. Research is being conducted to explore their benefits and risks, with careful regulation and oversight.
Key points:
- Psychedelics can alter perception and create new interventions for mental health without lasting change or addiction.
- They can be used in small doses as adjunctive treatments for therapy.
- Psychedelics increase connectivity between brain areas, similar to the dream state.
- This dream-like experience may relieve depression, but the exact mechanism is not fully understood.
- Psychedelics change the brain's threshold for becoming aware of incomplete or incorrect hypotheses.
- They may increase the flow of activity through brain circuits, potentially helping with depression.
- Psychedelics are being studied in the laboratory to determine their effects on specific brain cells and future representations.
MDMA
MDMA is a unique compound that increases brain levels of dopamine and serotonin simultaneously. It may be useful for treating trauma and PTSD. The experience of taking MDMA allows individuals to connect with others and learn from the experience. Dr. Karl Deisseroth discusses its use in psychiatry to facilitate deep connections and learning in patients.
Dr. Deisseroth’s New Book “Projections: A Story of Emotions”
Dr. Karl Deisseroth's new book, "Projections: A Story of Emotions," explores the future of psychiatry and brain science. Despite the tragic cases and weight on clinicians, Deisseroth remains optimistic about the potential for progress in understanding and healing the mind. The book aims to be accessible to everyone while staying rigorously close to the science. Deisseroth successfully balances scientific rigor with hope, showcasing the progress made and the beautiful trajectory of research in the field. The book is praised for its masterful storytelling and interesting insights, making it a must-read for those interested in the brain.
Key points:
- Dr. Karl Deisseroth's book, "Projections: A Story of Emotions," delves into the future of psychiatry and brain science.
- Despite the challenges faced by clinicians, Deisseroth maintains an optimistic outlook on the potential for advancements in understanding and treating the mind.
- The book strives to be accessible to a wide audience while maintaining scientific rigor.
- Deisseroth skillfully combines scientific rigor with hope, highlighting the progress and promising direction of research in the field.
- "Projections: A Story of Emotions" is praised for its captivating storytelling and intriguing insights, making it a must-read for those interested in the intricacies of the brain.
Connecting with Dr. Deisseroth on Twitter
Connecting with Dr. Deisseroth on Twitter allows for updates and information sharing. Dr. Deisseroth is dedicated to relieving suffering and appreciates community support. Listeners are encouraged to check out his book and support the podcast.