Episode 26: Dr. Karl Deisseroth: Understanding & Healing the Mind | Huberman Lab

Key Takeaways

  • Psychiatry is built around diseases diagnosed with words that don’t appear on scans or neuroimaging – unlike cardiology. We still have a long way to go in our understanding of the brain
  • Treatments in psychiatry can come with frustrations because the drugs and therapies with the best results are non-specific and often have the greatest side effects
  • The hope of optogenetics is to arm physicians with a true causal understanding of circuit underlying certain conditions of mental health disease and inform targeted treatments from there
  • The specificity of optogenetics is only useful if you have an understanding of how to use that information
  • There is a risk with all treatment, but it doesn’t appear that the risks in psychedelics exceed risks tolerated in other branches of medicine
  • “There’s a central cord of optimism that where we’re headed is not only possible but likely.” – Dr. Andrew Huberman


Dr. Karl Deisseroth, M.D., Ph.D. (@KarlDeisseroth), is a Clinical Psychiatrist and scientist who directs a bioengineering research laboratory at Stanford University School of Medicine. His work aims to understand and develop treatments for disorders of the mind such as depression, attention deficit disorders (ADHD & ADD), autism, schizophrenia, anxiety, eating disorders, borderline personality, and obsessive-compulsive disorder.

In this episode of Huberman Lab, Dr. Huberman and Dr. Deisseroth discuss research progress in developing cures for mental health disease and break down how the brain works in a healthy state and with emotional distress.

Host: Andrew Huberman (@hubermanlab)

Book: Projections: A Story of Human Emotions by Karl Deisseroth

The Art And Science Of Psychiatry

  • Neurologists use imaging to diagnose stroke, Alzheimer’s, brain damage, etc.
  • Psychiatry is built around diseases diagnosed with words that don’t appear on scans or neuroimaging
  • Future of mental health diagnoses: efforts are being made to look at brain waves and imaging but still has ways to go
  • What happens in the brain and psychiatric diseases is physical and measurables will likely be developed
  • Barriers to psychiatry: the stigma of mental health disorders prevents people from seeking treatment
  • Nuances in psychiatry: there is a difference between colloquial use of words and medical use of terminology
  • “You never really know what’s going on in the mind of another person.” – Dr. Karl Deisseroth
  • Sometimes other people observing someone is the best gauge of what’s happening in a person – e.g., husband may see that wife is sleeping more, eating less, and could be heading into depression
  • We actually know very little about the microcircuitry of the human brain

Successes In Psychiatric Treatments

  • Cognitive-behavioral therapy is extremely beneficial in treating panic disorder
  • Successful medications: anti-psychotic medications for schizophrenia – and many medications used for the treatment of various mental health conditions
  • Electroconvulsive therapy is extremely effective in severe depression as long as administered safely and in a controlled environment
  • The most frustrating thing about electroconvulsive therapy is the lack of specificity – you’re causing a brain-wide seizure – but it works
  • Frustration in treatment: some of the most anti-psychotic drugs, therapies, and medications are the least specific and have the greatest side effects but have the best results
  • Vagus nerve stimulation: a way to get into the brain without going directly into the brain
    • FDA approved for depression but is dose-limited because it stimulates everything nearby in the neck
    • Physicians can turn up the intensity in real-time remotely or in-person
  • Some psychiatrists sample small doses of drugs to understand what patients feel and side effects

What Will Move The Needle In Psychiatric Treatment?

  • Frustrations: (1) psychiatrists don’t have the level of understanding that other fields of medicine have – it isn’t like cardiology with a clear understanding of biology and physiology; (2) symptoms vary across people
  • Need clearer understanding: most psychiatric treatments have been discovered serendipitously
    • Anti-depression drugs were first created to cure tuberculosis
  • Need to identify circuits and patterns of activity driving activity in “healthy” state versus “non-healthy” state – to allow treatment along the path in a targeted manner

Defining Channelrhodopsins & Optogenetics

  • In plants channelrhodopsins function as light-gated ion channels – when a light particle hits them, ions rush in the pore
  • The movement of ions across the membrane is how the human brain and neural code for on and off
  • Mechanism of channelrhodopsins spurred the new field of optogenetics
  • Optogenetics: control neurons with algae protons (channelrhodopsins) using light – used to understand and manipulate sensation, cognition, action
  • Protocol of gene injection: channel rhodopsinsare are put into a vector (adeno-associated virus (AAV)) packaged with DNA and injected into a specific part of the body depending on the desired outcome
  • Protocol of light delivery: inject ½ mm light-emitting photon under the skin

Future Of Channelrhodopsins And Optogenetics

  • Early barriers to overcome: channelrhodopsins don’t move many ions because they have a small current so have to pack a lot in without damaging cells
  • 2007 put channelrhodopsins in mice to control actions in mice
  • 2021 put channelrhodopsins in the eyes of human beings and made a blind person see
  • The broader significance of optogenetics is understanding because once you know how circuitry works and what matters, treatment options become more grounded
  • In principle, channelrhodopsins will enable treatments to turn on or off specific regions of the brain which lead to depression, anxiety, etc.
  • Optogenetics would allow for more precise stimulation methods without affecting other parts of the body
  • The specificity of optogenetics is only useful if you have an understanding of how to use that information

Using And Understanding Cues From The Body

  • The eyes are rich in information – eye contact can be intense, mistimed, avoided, absent
  • The pairing of what’s going on in eyes with body language, verbal cues provides additional information
  • Psychiatrists learn to hone in on whatever data stream is given and can detect changes in tone of voice, eyes, etc. to inform diagnoses

Brain-Machine Interface

  • Brain-machine interface: devices that will stimulate patterns of activity of neurons
  • Using electrodes to gather information from neurons will allow us to understand what’s going on in the brain but still has risks
  • Could allow information collection and stimulation only when needed and with greater specificity
  • Identify patterns to target psychiatric interventions and timepoints


  • ADHD: symptoms of hyperactive or inattentive states; the key thing is that it’s present across different domains of life and isn’t specific to one setting
  • There is debate about what percentage of the population with symptoms should be treated with medicine
  • Working on quantitative EEG diagnosis
  • It’s debatable whether behaviors and interactions with the sensory world could induce or activate ADD or ADHD – it must be disrupting social or occupational functioning in non-adaptive ways

Psychedelic Medicine

  • Psychedelics create both an opportunity for therapeutic benefit and a risk
  • This is not the first time there has been a movement of psychedelics for medicinal purpose
  • Psychedelics alter the experience of reality in precise ways and there is an opportunity
  • There is a risk with all treatment, but it doesn’t appear the risks in psychedelics exceed the risks tolerated in other branches of medicine
  • Patients with depression are often stuck and can’t look to the future so they discount the value of their own action – psychedelics may improve this symptom by opening new paths or representations of seeing future or altered state
  • MDMA increases brain levels of dopamine and serotonin modulator which can be useful for the treatment of trauma
  • The brain learns from the experiences of psychedelics: psychedelics elicit experience at the moment and lasting impact after

Tips For Stress Mitigation And Improved Focus

  • Carve out protected time to just think – can even be while driving – any time to sit still
  • Make time for yourself without a phone, checking email, notifications, etc.
  • Learn to be physically still
  • Embrace that different stages of life come with unique needs

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Notes By Maryann

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