Dr. Andrew Huberman: Ketamine - Benefits and Risks for Depression, PTSD and Neuroplasticity (Huberman Lab Podcast)

The video by Dr. Andrew Huberman is about the benefits and risks of using ketamine for the treatment of depression, suicidality, and PTSD, as well as its potential for abuse. The video also discusses the mechanisms of action by which ketamine produces dissociative states and changes in neural circuitry. The video emphasizes the importance of understanding both the clinical benefits and risks of ketamine, and the long-term changes in the brain that can occur when using ketamine recreationally. The video also touches on the topic of neuroplasticity and the critical molecule brain-derived nootropic factor (BDNF) in the context of learning and memory.

This video by Andrew Huberman was published on Aug 7, 2023.
Video length: 01:42:41.

The Huberman Lab podcast episode titled "Ketamine:

Benefits and Risks for Depression, PTSD & Neuroplasticity" discusses the science and science-based tools for everyday life. The episode is about ketamine, a compound that is now being used clinically for the treatment of depression, suicidality, and PTSD, as well as a drug that is commonly abused. The episode emphasizes both the clinical benefits and the risks of using ketamine out of the appropriate clinical context. The episode also talks about neuroplasticity, or the nervous system's ability to change in response to experience, and brain-derived nootropic factor (BDNF), a critical molecule for all forms of learning and memory.

The episode is sponsored by Roca, which makes eyeglasses and sunglasses of the highest quality, and Eight Sleep, which makes Smart mattress covers with cooling, heating, and sleep tracking capacity.

• Ketamine is a fascinating compound used clinically for depression, suicidality, and PTSD.
• It is also commonly abused recreationally, with potential harms to the brain.
• Research has shown the acute or immediate effects of ketamine while under its influence.
• Ketamine can reduce the activity of neural circuits in various brain areas, including the gut.
• It can increase the activity of certain neurotransmitters, such as glutamate and GABA.
• Ketamine can also increase the production of brain-derived nootropic factor (BDNF), which is important for learning and memory.
• People can get addicted to ketamine, even if they find its effects compelling but degrading their overall life performance.
• Ketamine has established clinical uses for the treatment of depression, suicidality, and PTSD.
• The landscape around ketamine is different than it was 10 or 20 years ago, with increased interest surrounding it.

Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity | Huberman Lab Podcast - YouTube

Introduction

• Welcome to the Huberman Lab podcast
• Discussing science and science-based tools for everyday life
• Andrew Huberman is a professor of neurobiology and ophthalmology at Stanford School of Medicine
• Today's episode is about ketamine

Ketamine

• Ketamine is a fascinating compound
• Nowadays used clinically for depression, suicidality, and PTSD
• Also commonly abused recreationally
• Potential harms of using ketamine out of the appropriate clinical context

Clinical Benefits of Ketamine

• Research on the clinical benefits of ketamine
• Acute or immediate effects of ketamine while under its influence
• Treatment of depression, suicidality, and PTSD

Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity | Huberman Lab Podcast - YouTube

Risks of Ketamine

• Long-term changes in the brain that occur when using ketamine recreationally
• Importance of understanding both the clinical benefits and risks of ketamine

Neuroplasticity and BDNF

• Discussion of neuroplasticity, or the nervous system's ability to change in response to experience
• Talk about neuroplasticity not just in the context of ketamine but as a general theme for how the nervous system changes anytime you learn
• Learning about bdnf, or brain-derived nootropic factor, a critical molecule for all forms of learning and memory

Introduction

• The video is about the benefits and risks of using ketamine for the treatment of depression, suicidality, and PTSD, as well as its potential for abuse.
• The video also discusses the mechanisms of action by which ketamine produces dissociative states and changes in neural circuitry.
• The video emphasizes the importance of understanding both the clinical benefits and risks of ketamine, and the long-term changes in the brain that can occur when using ketamine recreationally.
• The video touches on the topic of neuroplasticity and the critical molecule brain-derived nootropic factor (BDNF) in the context of learning and memory.

Ketamine and PCP

• Ketamine is very similar to another drug called PCP or phen cycladine which goes by the street names angel dust or Sherm.
• PCP and ketamine act similarly in the brain as dissociative anesthetics.
• Ketamine is nowadays usually used for its benefits in the treatment of depression, suicidality, and PTSD.
• However, ketamine also has a high potential for abuse and can lead to addiction.

Ketamine and Recreational Use

• Ketamine is an incredible drug that is very similar to PCP.
• There is crossover between the clinical uses of ketamine for treatment of depression and its recreational use.
• If there is increased access to a drug like ketamine, there is also an increase in the number of people using it recreationally.
• Some people do get addicted to ketamine, which can degrade their overall life performance.

Ketamine and Addiction

• People can get addicted to ketamine, even if they find its effects compelling but degrading their overall life performance.
• Ketamine does have established clinical uses for the treatment of depression, suicidality, and PTSD.
• The landscape around ketamine is different than it was 10 or 20 years ago.
• Ketamine is now being prescribed widely and has all this interest surrounding it.

History of Depression and Its Treatment

• The so-called monoamine hypothesis of depression was developed in the middle of the last century.
• Monoamines are neurotransmitters that change the activity of neural circuits in the brain and body.
• Monoamines include things like serotonin, dopamine, and norepinephrine.
• Monoamines are synthesized from amino acids.

The Benefits and Risks of Ketamine for Depression, PTSD, and Neuroplasticity

• Ketamine is a dissociative anesthetic that has been studied for its abuse and anesthetic properties.
• It has been found to have dissociative states and changes in neural circuitry.
• Ketamine can reduce the activity of neural circuits in various brain areas, including the gut.
• Serotonin, dopamine, and norepinephrine play important roles in the body, but there is little evidence that deficiencies in these monoamines cause depression.
• Drugs that increase certain monoamines, such as Prozac or Zoloft, can provide relief for certain symptoms of depression in some people, but they have side effects and only work in about 40% of depressed people.

Other Compounds to Treat Depression

• Other compounds, such as ketamine, are being studied to treat depression without creating similar side effect profiles.
• Ketamine has helped a tremendous number of people get relief from depressive symptoms and ward off suicidality.
• However, there are also great number of people who have experienced a lot of side effects and problems from these drugs.
• The desire is to find other compounds that can treat depression without creating similar side effect profiles.

Ketamine as a Treatment for Depression, PTSD, and Neuroplasticity

• Ketamine is a dissociative anesthetic that has been studied for its abuse and anesthetic properties.
• It has been found to have dissociative states and changes in neural circuitry.
• Ketamine can reduce the activity of neural circuits in various brain areas, including the gut.
• Serotonin, dopamine, and norepinephrine play important roles in the body, but there is little evidence that deficiencies in these monoamines cause depression.
• Drugs that increase certain monoamines, such as Prozac or Zoloft, can provide relief for certain symptoms of depression in some people, but they have side effects and only work in about 40% of depressed people.

Ketamine's Mechanisms of Action

• Ketamine produces dissociative states and changes in neural circuitry.
• It reduces the activity of neural circuits in various brain areas, including the gut.
• Ketamine can increase the activity of certain neurotransmitters, such as glutamate and GABA.
• It can also increase the production of brain-derived nootropic factor (BDNF), which is important for learning and memory.

Ketamine's Risks and Side Effects

• Ketamine can have a lot of side effects and problems, including dry mouth, reductions or increases in appetite, vast reductions in libido, and changes in sleep patterns.
• It can also cause hallucinations, anxiety, and confusion.
• Ketamine can be addictive and can lead to dependence.
• It can also have long-term changes in the brain that can occur when using ketamine recreationally.

Ketamine and Pre-clinical Models of Depression

• Ketamine is a dissociative anesthetic that can be taken sublingually, injected intravenously, or intramuscularly.
• The speed of onset and type of effects produced in the brain and body vary depending on the method of administration.
• In the early 1990s, laboratories studying animal models of depression discovered a pre-clinical model called the model of learned helplessness.
• This model involves putting a rat or mouse into water and observing when it gives up trying to save itself.
• Researchers used this model to test different drugs and establish which dosages allowed animals to fight for their life longer when placed into water.

Ketamine and NMDA Receptors

• Ketamine is an NMDA receptor antagonist or blocker.
• It has the property of overcoming learned helplessness or a sense of hopelessness in animals.
• Researchers were surprised to discover that ketamine allowed animals to fight for their life for longer.
• Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist or blocker.
• An agonist is something that promotes the activity of a receptor, while an antagonist blocks it.

Ketamine and Depression

• The model of learned helplessness is a prominent pre-clinical model of depression.
• Researchers used this model to test different drugs and establish which dosages allowed animals to fight for their life longer when placed into water.
• Ketamine is an NMDA receptor antagonist or blocker.
• It has the property of overcoming learned helplessness or a sense of hopelessness in animals.
• Researchers were surprised to discover that ketamine allowed animals to fight for their life for longer.

Ketamine and Human Depression

• The model of learned helplessness is a prominent pre-clinical model of depression.
• Researchers used this model to test different drugs and establish which dosages allowed animals to fight for their life longer when placed into water.
• Ketamine is an NMDA receptor antagonist or blocker.
• It has the property of overcoming learned helplessness or a sense of hopelessness in animals.
• Researchers were surprised to discover that ketamine allowed animals to fight for their life for longer.

Ketamine and Major Depressive Episode

• The model of learned helplessness is a prominent pre-clinical model of depression.
• Researchers used this model to test different drugs and establish which dosages allowed animals to fight for their life longer when placed into water.
• Ketamine is an NMDA receptor antagonist or blocker.
• It has the property of overcoming learned helplessness or a sense of hopelessness in animals.
• Researchers were surprised to discover that ketamine allowed animals to fight for their life for longer.

Ketamine and Antidepressant Effects

• Ketamine is an NMDA receptor antagonist or blocker.
• The NMDA receptor is critical for neuroplasticity.
• Despite blocking the receptor that's critical for neuroplasticity, ketamine is allowing animals to swim longer.
• Ketamine is relieving depression in preclinical animal models.
• Clinicians tried ketamine in depressed patients as a means to relieve depression and it had remarkable effects.

Ketamine and Clinical Use

• Ketamine was first used for the treatment of depression in the year 2000.
• Drugs like Prozac and similar SSRIs were popular at the time, but some people were getting relief with a lot of side effects.
• A lot of people who were taking these drugs were not getting relief.
• There was a real urgent need to find other drugs for the treatment of depression.
• Ketamine, at least based on its apparent profile of being a dissociative anesthetic, would seem like the last drug that you'd want to use to treat depression.

Ketamine and Dissociative States

• Ketamine dissociates people even when used for the treatment of depression.
• Dissociation is a symptom of depression.
• One small study found that intravenous injections of ketamine at a dosage of half a milligram per kilogram of body weight effectively relieved depression in seven subjects with major depression.
• The effects of ketamine took place within minutes and peaked about 45 minutes to an hour after injection.
• The total effects of the drug in terms of euphoria were effectively over by about two hours.

Ketamine and Neuroplasticity

• The NMDA receptor is critical for neuroplasticity.
• Ketamine blocks the NMDA receptor, which is critical for neuroplasticity.
• Despite blocking the receptor that's critical for neuroplasticity, ketamine is allowing animals to swim longer.
• Ketamine is relieving depression in preclinical animal models.
• Clinicians tried ketamine in depressed patients as a means to relieve depression and it had remarkable effects.

Ketamine for Depression

• Ketamine produces dissociative, euphoric, dreamlike effects that take place very quickly and are very salient.
• People experience immediate relief from their depression after taking ketamine, which persists for several days after treatment.
• The antidepressant effects of ketamine appear to be short-lived, typically lasting only a few days.
• Ketamine is an attractive drug for the treatment of depression, especially depression that has not responded to other forms of treatment.
• Rapid treatments for depression, such as ketamine, are important for managing depression, especially for those who suffer from it for an extended period of time.

Ketamine for PTSD and OCD

• Ketamine has been shown to be useful for the treatment of PTSD and OCD.
• Ketamine has also been shown to be effective in treating anxiety and various forms of substance addiction.

Ketamine and Neuroplasticity

• Ketamine has been shown to have broad application and to be very successful for the treatment of a lot of major psychiatric challenges.
• Ketamine has been shown to produce changes in neural circuitry that are associated with neuroplasticity.

Ketamine and Addiction

• Ketamine has been shown to be useful for the treatment of substance addiction.

Ketamine and Depression

• Ketamine can provide relief from depression immediately and in the days after treatment.
• There is some durability to the effect, meaning that if people take ketamine twice a week for three weeks, they can get ongoing relief from their depressive symptoms for months or more before repeating the treatment.
• Studies have shown that ketamine can provide relief from depression by at least two and probably three different mechanisms.
• One mechanism induces relief from depression very quickly and is associated with the euphoric, dissociative dreamlike state experienced under the influence of ketamine.
• Another mechanism provides relief from depression in the days and weeks that follow ketamine treatment.

Ketamine and Neuroplasticity

• Ketamine blocks the NMDA receptor, which is critical for many forms of neuroplasticity.
• Relief from depression is all about neuroplasticity.

Ketamine and Addiction

• Ketamine can become a drug of abuse and be habit-forming or addicting.
• People taking ketamine every week may not be feasible due to the risk of addiction.

Ketamine and Recreational Use

• Ketamine can produce a dissociative state, taking people out of their normal daily routine.
• Recreational use of ketamine can lead to long-term changes in the brain.

Section 1: Introduction to NMDA Receptors

• NMDA receptors are a type of receptor found on the surface of neurons in the brain.
• They bind glutamate, a molecule made in the brain, and activate other neurons.
• Glutamate is an excitatory neurotransmitter.
• There are many different receptors for glutamate, but the NMDA receptor is unique in that it requires a lot of glutamate and electrical activity to activate.

Section 2: NMDA Receptors and Neuroplasticity

• NMDA receptors are involved in neuroplasticity, the brain's ability to change and adapt.
• Glutamate binding to NMDA receptors is an and gate, meaning that two things must be present in order for neuroplasticity to occur.
• The NMDA receptor is a high-affinity receptor, meaning it knows how to seek out and bind to its target.
• The NMDA receptor is primarily activated by unusually high or frequent levels of electrical activity.

Section 3: NMDA Receptors and Everyday Life

• NMDA receptors are involved in everyday activities such as moving arms and legs.
• Glutamate is involved in the process of motor coordination of limbs.
• Typical levels of activity are sufficient for everyday activities.
• If someone were to perform a specific motor limb movement for an extended period of time, the neurons involved in generating that movement would become more active and the NMDA receptor would be activated, leading to changes in the nervous system.

Section 4: NMDA Receptors and Ketamine

• Ketamine has a very high affinity for the NMDA receptor, meaning it can easily bind to it.
• When ketamine is introduced into the bloodstream, it can cross the blood-brain barrier and bind to NMDA receptors in the brain.
• Ketamine can activate the NMDA receptor even at low levels of glutamate and electrical activity.
• Ketamine can cause changes in the nervous system that are similar to those seen in neuroplasticity.

The NMDA Receptor and Neuroplasticity

• The NMDA receptor is activated by infrequent or unusual patterns of activity.
• It can recruit other glutamate receptors to the cell surface, allowing behavior to occur without engaging neuroplasticity processes.
• Activation of the NMDA receptor only occurs under conditions of unusually high or simply unusual patterns of activity.
• The NMDA receptor controls neural activity in the immediate sense, but also engages gene expression and introduces new receptors to the cell.
• The NMDA receptor is critical at detecting unusual activity and making changes to cells so they can respond to that activity.

Ketamine and Neuroplasticity

• Ketamine is an NMDA receptor blocker and antagonist.
• The changes in the brain that underlie the transition from a depressed state to a non-depressed state involve neuroplasticity.
• Ketamine works by blocking the NMDA receptor, which is critical at detecting unusual activity and making changes to cells.
• There are essentially two major types of neurotransmission in the brain: excitatory and inhibitory.
• Excitatory neurotransmission involves neurons that release neurotransmitter into the synapse, making other neurons electrically active.

Ketamine and Seizures

• Seizures are essentially runaway excitation in the brain.
• A small region of the brain becomes especially electrically active and then it spreads out from that foci.
• Inhibitory neurons and excitatory neurons are in a push-pull that keeps the brain in balance.
• Ordinarily inhibitory neurons suppress the activity of many neurons, preventing seizures.
• Ketamine can disrupt this balance, leading to seizures.

Neuron Communication and NMDA Receptors

• Neurons communicate through excitatory and inhibitory signals.
• Excitatory neurons stimulate the electrical activity of other neurons.
• Inhibitory neurons inhibit or suppress the activity of other neurons.
• Both excitatory and inhibitory communication between neurons is necessary at all times.
• The NMDA receptor is critical for neuroplasticity.

Watch the video on YouTube:
Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity | Huberman Lab Podcast - YouTube