00:00:00 Introduction

Overview: Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine, introduces the topic of dopamine and its relation to motivation, desire, craving, satisfaction, wellbeing, and addiction. He promises to dispel common myths about dopamine and provide tools for leveraging it to sustain energy, drive, and motivation.

00:01:02 Dispelling Myths About Dopamine

Overview: Andrew Huberman discusses common myths about dopamine and how it actually works. He covers the biology and psychology of dopamine as well as neural circuits and dopamine schedules. He explains how various things like food, drugs, caffeine, pornography, and plant-based compounds can change our baseline levels of dopamine.

00:02:10 Achieving High Increases in Dopamine Through Behaviors

Overview: Andrew Huberman shares a fascinating result published in the European Journal of Physiology that shows how human subjects exposed to cold water experience rapid increases in norepinephrine (adrenaline), epinephrine (adrenaline), and dopamine. The dopamine release continues to rise even after getting out of the cold water and reaches 250% above baseline. This sustained increase in dopamine can improve sense of wellbeing, cognition, clarity of mind.

0:04:08 Achieving the Sweet Spot in Sports

Overview: In this section, the speaker talks about achieving a highly alert but calm state of mind that is ideal for sports. He explains how cold water exposure can help people achieve this state of mind by increasing dopamine levels and limiting cortisol release.

Cold water exposure done correctly can help people achieve an ideal state of mind for sports.
Increases in dopamine levels from cold water exposure last a long time.
The speaker will later detail a study on cold water exposure, including its duration, variations, and effects on different subjects.
The speaker will also discuss compounds and supplements that can increase dopamine levels.

0:04:53 Disclaimer and Introduction to Sponsors

Overview: In this section, the speaker provides a disclaimer that his podcast is separate from his teaching and research roles at Stanford. He also introduces two sponsors for the podcast - Roka and InsideTracker.

The podcast is separate from the speaker's teaching and research roles at Stanford.
The podcast aims to provide zero-cost information about science-related tools to the general public.
Roka makes high-quality sunglasses and eyeglasses designed with the visual system biology in mind.
Roka glasses are lightweight, won't slip off during exercise, and have great aesthetics.
Listeners can use code "Huberman" at checkout on www.roka.com to save 20% off their first order.
InsideTracker is a personalized nutrition platform that analyzes data from blood and DNA to help users understand their bodies better.
Regular blood work combined with modern DNA tests can help optimize health factors such as hormones and metabolism.
InsideTracker offers home or clinic-based testing services.

that you think is giving you a dopamine hit, what's actually happening is that your brain is experiencing a peak in dopamine above its baseline level.

0:10:55 What Happens Afterward

Overview: The baseline level of dopamine drops after a peak in dopamine, which influences how much dopamine will generally be circulating afterward.

0:11:01 Tonic and Phasic Release of Dopamine

Tonic release is the low level baseline that's always there circulating, released into your brain all the time.
Phasic release are peaks that ride above that baseline.
These two things interact and influence how much dopamine will generally be circulating afterward.

0:11:50 Importance of Dopamine

Dopamine has everything to do with how you feel right now as you're listening to this.
It has everything to do with how you will feel an hour from now, your level of motivation, desire, and willingness to push through effort.
The level of dopamine is the primary determinant of how motivated we are, how excited we are, and our willingness to lean into life and pursue things.

0:12:46 Neuromodulators vs Neurotransmitters

Neuromodulators coordinate neural circuits while neurotransmitters mediate local communication between neurons.
Dopamine release changes the probability that certain neural circuits will be active and others inactive.

0:13:47 Functions of Dopamine

Dopamine is responsible for motivation, drive, craving, time perception, movement control.
It is important to access increases in dopamine at different timescales for sustained effort and happiness over long periods.
Depletion or death of dopamine neurons can lead to shaky movements and challenges in initiating movement seen in Parkinson's or Lewy bodies dementia.

0:15:01 Parkinson's and Lewy Body Dementia

Overview: People with Parkinson's and Lewy body dementia experience drops in motivation and mood. Proper treatment can help recover fluidity of movement and improve psychological well-being.

0:15:27 Neural Circuits for Dopamine

Overview: There are two main neural circuits in the brain that dopamine uses to exert its effects. The mesocorticolimbic pathway influences motivation, drive, and craving, while the nigrostriatal pathway is mainly for movement.

0:18:11 Release of Dopamine

Overview: The way dopamine is released in the brain and body can differ.

0:18:25 Introduction to Synapses and Dopamine

Overview: This section discusses the role of synapses in communication between neurons and how dopamine can influence this communication.

Neurons communicate through synapses, which are spaces between nerve cells.
One neuron can cause another neuron to become electrically active or less electrically active through the release of chemicals called neurotransmitters.
Dopamine is a neurotransmitter that can influence other neurons at a local scale or a broad scale through volumetric release.
Increasing dopamine levels through drugs or supplements can affect both local and volumetric release, but may make it harder to sustain dopamine release over long periods of time.
The height of the peak of dopamine relative to the baseline is important for experiencing pleasure from things.

0:21:35 Optimizing Peak-to-Baseline Ratio

Overview: This section discusses how to optimize the peak-to-baseline ratio for experiencing pleasure from things.

There is a better way to increase dopamine levels than just taking drugs or supplements, as this may make motivation short-lived.
Two main neural circuits related to dopamine are movement and motivation/craving.
Dopamine communicates with other neurons through local synaptic release or more broad volumetric release.
The duration of action for dopamine also plays a role in its effects.

0:22:27 G protein-coupled receptors

Overview: This section discusses the two main ways neurons communicate and how dopamine works through G protein-coupled receptors.

Neurons mainly communicate through fast electrical synapses ionotropic conduction, where one neuron activates another by opening little holes in that neuron and allowing ions to rush in.
Dopamine works through slower G protein-coupled receptors, where dopamine is released into the synapse and binds to the next neuron, setting off a cascade of effects.
G protein-coupled receptors can have multiple cascades of effects and even impact gene expression at some level.

0:23:30 Dopamine's communication process

Dopamine doesn't communicate through fast ionotropic conduction like other neurons. It works through slower G protein-coupled receptors.
Some dopamine will bind to the postsynaptic neuron, setting off a cascade of effects that can impact gene expression and change how well or poorly that cell responds to the same signal in the future.
Dopamine has two pathways for communication - one for movement and one for motivation and craving.
Neurons that release dopamine also co-release glutamate, an excitatory neurotransmitter that stimulates neurons to be electrically active.

0:25:25 The stimulating effect of dopamine

Dopamine is responsible for movement, motivation, drive, and general action because it releases an excitatory neurotransmitter called glutamate.
Dopaminergic transmission tends to stimulate sympathetic arousal.

0:26:10 Understanding Dopamine

Overview: In this section, the speaker discusses dopamine and its role in motivating individuals to pursue things outside of themselves. Dopamine is a universal currency in all mammals, but especially in humans for moving us toward goals.

Dopamine is released when we look outside ourselves and pursue things outside ourselves.
It is responsible for our desire to crave things outside ourselves.
The pleasure that arrives from achieving things also involves dopamine, but it's mainly the consequences of other molecules.
A low dopamine state can make you feel lethargic and lazy with no motivation or drive.
A high dopamine state can make you feel excited, motivated, even if you're a little scared to do something.
Dopamine is subjective and depends on how much dopamine was in our system compared to how much was there a few minutes ago and how much we remember enjoying a particular experience of the past.
Your experience of life and your level of motivation depend on how much dopamine you have relative to your recent experience.

0:28:06 Misconceptions about Dopamine Hits

Overview: In this section, the speaker talks about misconceptions around "dopamine hits" and explains that how much dopamine you experience from something depends on your baseline level of dopamine when you arrive there and your previous dopamine peaks.

The general language around "dopamine hits" neglects the fact that if you scroll social media or see something you really like, there's an increase in dopamine. But then if you get to something else that's not as interesting, the increase in dopamine decreases.
How much dopamine you experience from something depends on your baseline level of dopamine when you arrive there and your previous dopamine peaks.
Repeatedly engaging in something that you enjoy increases your threshold for enjoyment.

0:29:45 Controlling Dopamine Release

Overview: This section discusses how we can modulate and control our own dopamine release for optimal motivation and drive. The speaker mentions a detailed review on the biology of dopamine transmission, which they will link in the video's caption.

0:30:26 Anecdotes Illustrating the Biology of Dopamine

Overview: The speaker shares two anecdotes that illustrate how profoundly dopamine can shape our experience.

0:30:47 Tragic Outbreak of Parkinsonian Symptoms

In the 80s, there was an outbreak of what looked like Parkinsonian symptoms in a young population.
Street laboratories were trying to make a drug called MPPP, which is an opioid light compound.
Heroin addicts seeking heroin bought what they thought was MPPP but ended up taking MPTP instead.
MPTP can arise in the synthesis of MPPP and kills dopaminergic neurons of both nigrostriatal pathway involved in generating movement and mesocorticolimbic pathway involved in motivation and drive.
A large number of young people who were opioid addicts became completely paralyzed, unable to speak or move. They had no motivation or drive and were locked in frozen. Sadly, this is irreversible.

0:33:03 Speaker's Personal Experience with Understanding Dopamine Levels

The speaker was in college when the MPTP outbreak happened but had no understanding at the time about high or depleted levels of dopamine.
There was no reason why they should have that understanding as they had only experienced different pleasures.

0:33:28 Understanding the Importance of Dopamine

Overview: In this section, the speaker shares his personal experience with a stomach bug called Giardia and how it led to a profound understanding of dopamine's importance. He explains that dopamine is one of the most powerful molecules in our body and plays a crucial role in movement, mood, and motivation.

The speaker had Giardia which caused terrible diarrhea and dehydration.
In the emergency room, he was given Thorazine, an antipsychotic drug that blocks dopamine receptors.
The injection made him feel overwhelmingly sad and depressed.
He asked for l-DOPA to get his dopamine levels back up again, which made him feel fine within minutes.
This experience gave him tremendous sensitivity to the fact that dopamine is perhaps one of the most powerful molecules in our body.
Even subtle fluctuations in dopamine can shape our perception of life and what we're capable of feeling.
The speaker emphasizes the importance of guarding our dopamine levels and understanding them to maintain a healthy baseline while still being able to access peaks in dopamine.

0:37:04 Dopamine and Epinephrine

Overview: This section discusses the relationship between dopamine and epinephrine, two chemicals in the brain that are closely related. Dopamine is responsible for coloring the subjective experience of an activity to make it more pleasurable, while epinephrine is more about energy. When dopamine is released in the brain, epinephrine becomes one of excitement.

All individuals have different baseline levels of dopamine, which can be influenced by genetics and previous experiences.
Epinephrine (adrenaline) is the main chemical driver of energy and is necessary for any activity.
Dopamine and epinephrine are closely related family members that tend to work together to make individuals seek out certain things.
Activities or substances that increase dopamine levels include those that are pleasurable or exciting, such as exercise, food, drugs, or sex. The amount of dopamine released depends on the specific activity or substance.

there's probably a rational explanation for why I like them. But the subjective experience of liking them is what matters here.

0:41:04 Typical Things That Increase Dopamine

Overview: This section discusses various things that people do, eat, or take that can increase dopamine levels in the brain. The speaker notes that some of these things are good for us while others are not.

Chocolate increases baseline dopamine levels by 1.5 times but only temporarily.
Pursuing and engaging in sex doubles baseline dopamine levels.
Nicotine from smoking increases dopamine levels by 2.5 times above baseline but the effect is short-lived.
Cocaine increases dopamine levels in the bloodstream by 2.5 times above baseline.
Amphetamine increases dopamine levels in the bloodstream by 10 times above baseline.
Exercise can increase dopamine levels depending on how much someone enjoys it, with running being similar to sex in its effects on dopamine.

0:44:13 Importance of Prefrontal Cortex

Overview: The prefrontal cortex plays an important role in assigning a subjective experience to something and rationalizing our preferences.

The prefrontal cortex is involved in thinking, planning, and assigning a rational explanation to something.
It also assigns a subjective experience to something, such as liking a particular pen or enjoying a certain form of exercise.

0:44:55 The Impact of Thoughts on Dopamine Release

Overview: Our thoughts and what we say about something can have a profound impact on its rewarding or non-rewarding properties. Journaling, practicing appreciation, or thinking about an aspect of something enjoyable can increase the amount of dopamine released.

People who hate exercise can think about some aspect of it that they enjoy to increase dopamine release.
Saying you hate something but love the reward afterward will not make you like it more and may actually undermine dopamine release.
Certain chemicals like chocolate, sex, nicotine, cocaine, and amphetamine cause universal increases in dopamine. However, subjective activities like exercise or working through challenges in relationships will vary in their effect on dopamine release.
Caffeine increases dopamine to a modest extent compared to other substances but regular ingestion upregulates certain dopamine receptors, making you able to experience more of its effects.
Different compounds like alcohol and nicotine or caffeine and nicotine can synergize to give bigger dopamine increases.

0:48:35 Energy Drinks and Dopamine

Overview: In this section, the speaker discusses how people consume energy drinks or pre-workouts to get a dopamine rush for motivation and drive. However, relying on these substances too often can lead to a decrease in dopamine release and motivation.

People drink canned energy drinks or pre-workouts to stimulate dopamine release.
Exercising also helps increase dopaminergic experience.
Relying on substances and activities that lead to big increases in dopamine can create severe issues with motivation and energy.
Layering together multiple things that lead to big increases in dopamine can also have negative effects.
Taking occasional pre-workout or drinking coffee before working out is okay, but doing it too often can decrease motivation and drive.

0:49:56 Understanding Dopamine Peaks vs Baseline

Overview: The speaker explains why we have a dopamine system and how it relates to seeking resources such as food, water, shelter, social connection, etc. Dopamine is the universal currency of forging and seeking. Understanding the relationship between baseline levels of dopamine and peaks is crucial for leveraging it for our own purposes.

Dopamine is the universal currency of forging and seeking.
Seeking things that make us feel good and avoiding things that don't make us feel good are related to forging and seeking resources.
Dopamine has a baseline level as well as peaks related in some direct way.
Understanding the relationship between baseline levels of dopamine and peaks is crucial for leveraging it for our own purposes.

0:52:05 Foraging and Dopamine

Overview: This section discusses how dopamine drives the foraging process and how it affects our behavior.

Dopamine is responsible for driving us to go out and look for things, whether it's hunting or gathering.
When we find something rewarding, such as a good berry or successful hunt, we experience a release of dopamine.
However, the level of dopamine drops below baseline after achieving the reward to motivate us to continue seeking more rewards.
The extent to which dopamine drops below baseline is proportional to how high the peak was.

0:53:29 Post-Reward Dopamine Drop

Overview: This section explains why our level of dopamine drops below baseline after achieving a reward.

Contrary to what we might think, crossing the finish line of a marathon or achieving any other big win doesn't keep our level of dopamine elevated.
Our level of dopamine drops below baseline after achieving a reward because if it stayed elevated, we would never continue seeking more rewards.
The drop in baseline dopamine can lead to postpartum depression or feeling lower than usual after experiencing a big win.
Engaging in something enjoyable repeatedly can cause it to lose its excitement due to this drop in baseline dopamine.

0:55:38 The Relationship Between Dopamine and Addiction

Overview: In this section, Dr. Huberman discusses how dopamine affects our pleasure and pain balance, and how indulging in behaviors that increase dopamine can lead to addiction.

Consuming things and doing things that increase our dopamine levels can make us feel good.
However, the drop in baseline after any peak in dopamine is substantial.
We all have a sort of dopamine set point.
Continuously indulging in behaviors that increase our dopamine levels can lead to addiction.
Even for people who aren't addicted, the drop in baseline after any peak in dopamine is substantial.
This drop governs whether or not we are going to feel motivated to continue pursuing other things.

0:56:32 Finding Balance with Dopamine

Overview: In this section, Dr. Huberman talks about ways to work with the pleasure-pain balance associated with seeking something we really like.

Dr. Anna Lembke's book "Dopamine Nation" focuses on these dopamine schedules and the relationship between peaks and baselines of dopamine.
There's a pleasure-pain balance when we seek something we really like or indulge in it.
The pleasure and pain are governed by dopamine to some extent.
When you engage in an activity or ingest something that increases your dopamine levels, the levels go up substantially.
The pain comes from the lack of dopamine that follows as a result of depleted synaptic vesicles containing dopamine.
There's only a pool of synthesized dopamine available for release called readily releasable pool.

0:59:37 Understanding the Pleasure-Pain Balance

Overview: This section discusses how dopamine affects our pleasure-pain balance and how addiction can occur when pursuing activities that lead to huge increases in dopamine.

Dopamine depletion leads to a drop in baseline, causing people to feel lousy.
Pursuing dopamine-releasing activities or substances again mistakenly brings up the baseline, but it actually depletes dopamine more and more.
Addiction is a progressive narrowing of things that bring pleasure.
People lose interest in other aspects of their life and eventually stop getting dopamine release from that activity, leading to severe depression.

1:02:02 Balancing Activities That Release Dopamine

Overview: This section talks about balancing activities that release dopamine to avoid addiction.

Even if someone only consumes alcohol one or two nights a week, they may be spiking their dopamine with food during the middle of the week.
Dopamine is evoked by all activities, so even seemingly balanced activities can still contribute to an imbalance in the pleasure-pain balance.

1:03:21 The Relationship Between Dopamine Peaks and Baseline

Overview: In this section, the speaker discusses how dopamine levels can drop imperceptibly over time due to engaging in activities that spike dopamine too frequently. This can lead to a decrease in energy and motivation.

Spiking dopamine through various activities throughout the week can cause a progressive drop in baseline.
This drop can be very subtle but eventually reaches a threshold where pleasure cannot be derived from anything anymore.
This looks similar to severe addictions like cocaine and amphetamine which lead to big spikes in dopamine followed by severe drops in baseline.
Understanding the relationship between peaks and baseline is important for making good choices to maintain or raise dopamine levels while still achieving feelings of elevated motivation, desire, and craving.
Dopamine is what drove the evolution of our species and drives life progression.

1:05:28 What To Do If You Experience A Drop In Baseline Level Of Dopamine

Overview: The speaker provides an example of someone who became addicted to video games and decided to do a 30-day complete fast from phone, video games, and social media. After completing the fast, his levels of concentration and overall mood improved.

Replenishing the releasable pool of dopamine involves not engaging in dopaminergic seeking behaviors.
People typically want to stop engaging in these behaviors when their dopamine is depleted.
Doing a complete fast from phone, video games, and social media for 30 days can help replenish dopamine levels.
After completing the fast, concentration levels improved and there was no need for ADHD treatment.

1:07:11 ADHD Treatment and Dopamine Depletion

Overview: The speaker discusses the misdiagnosis of ADHD due to dopamine depletion caused by overindulgence in other activities. They suggest pursuing clinical treatment if there is a need, but for those with addictive tendencies, limiting interactions with dopamine-evoking behaviors or substances is the path forward.

1:07:46 Engaging in Dopamine-Evoking Activities

The speaker talks about engaging in activities that evoke dopamine, such as chocolate, coffee, sex, reproduction (in a healthy and appropriate context), food, and exercise. They classify drugs of abuse like cocaine and amphetamine as bad. The key to engaging in these activities healthily is through intermittent release of dopamine. Expecting or chasing high levels of dopamine release every time we engage in these activities can lead to a drop in baseline.

1:09:02 Intermittent Reward Schedules

Intermittent reward schedules are central to keeping people motivated and pursuing highly engaging activities like gambling, social media use, or pursuing elusive partners. This schedule is also present in our evolutionary adaptive scenario where not every pursuit played out. Dopamine reward prediction error occurs when we expect something to happen and are highly motivated to pursue it. If it happens great, we get the reward (dopamine), making us more likely to engage in that behavior again. The best schedule for exporting this reinforcement schedule to other activities is an intermittent one where dopamine sometimes arrives at different amounts intermittently.

1:11:00 The Importance of Intermittent Reinforcement

Overview: In this section, the speaker discusses the importance of being careful about allowing oneself to experience huge peaks in dopamine when experiencing a win. He explains that by layering together all these things to try and achieve that dopamine release, you're actually increasing the number of conditions required to achieve pleasure from that activity again.

It is important not to experience huge peaks in dopamine unless you're willing to suffer the crash that follows and waiting a period of time for it to come back up.
To maintain motivation for school, exercise, relationships or pursuits of any duration in kind, it is crucial to make sure that the peak in dopamine doesn't occur too often.
Vary how much dopamine you experience with each engagement in that activity.

1:11:13 Practical Application

Overview: The speaker provides practical examples on how one can apply intermittent reinforcement.

If you enjoy exercise, make it pleasurable by giving yourself your favorite cup of coffee first or listening to your favorite music.
However, there's also a version where sometimes you don't do the dopamine-enhancing activities. You just do the exercise without expecting dopamine to arrive through some exogenous source as well.
Start paying attention to the amount of dopamine and excitement and pleasure that you achieve with those activities and start modulating them somewhat at random.

1:13:08 Intermittent Property Woven into Activities

Overview: The speaker explains how some activities naturally have this intermittent property woven into them.

Some classes are more enjoyable than others; we don't always get straight A's or get rewarded with the outcome we would like.
Your ability to experience motivation and pleasure for what comes next is dictated by how much motivation and pleasure and dopamine you experienced prior.

1:14:01 Modulating Dopamine Release

Overview: The speaker suggests ways on how one can modulate their dopamine release.

Remove some of the dopamine-releasing chemicals that you might take prior. Maybe remove them every time but then introduce them once in a while.
Sometimes do things socially that you enjoy doing socially; sometimes do the same thing alone.

1:14:40 Maintaining a Healthy Baseline of Dopamine

Overview: The importance of maintaining a healthy baseline level of dopamine is discussed, and a tool for implementing intermittent schedules is suggested. The use of smartphones in relation to dopamine levels is also explored.

It's important not just to achieve peaks in dopamine but also to maintain a healthy baseline level.
A tool for implementing intermittent schedules can be flipping a coin before engaging in activities that support dopamine levels.
Smartphones are commonly used for various activities that layer in dopamine, potentially leading to disruptions or lowering of baseline levels.
Personal example given about how bringing the phone to workouts led to distraction and loss of interest over time due to too many layered-in activities.

1:15:26 Smartphones and Dopamine

Smartphones are an interesting tool for dopamine due to their ability to layer in various activities.
Using smartphones while engaging in other activities can lead to disruptions or lowering of baseline levels.
Levels of depression and lack of motivation are on the increase, potentially related to interactions with digital technology.

1:16:31 Personal Example

Personal example given about how bringing the phone to workouts led to distraction and loss of interest over time due to too many layered-in activities.
A rule was implemented where the phone is not allowed during workouts, including no music from the phone or texting.

1:18:16 The Impact of Dopamine on Enjoyment

Overview: In this section, the speaker discusses how dopamine affects our enjoyment of activities and how overstimulation can lead to a decrease in pleasure.

Achieving a great dopamine increase through technology such as phones and social media can remove the excitement and pleasure from activities we engage in.
Removing multiple sources of dopamine release from activities we want to enjoy or continue to enjoy can help us appreciate them more.
Using stimulants every time we engage in an activity we want to enjoy or be motivated at, except for caffeine, can reduce satisfaction and joy over time.
Energy drinks, pre-workout drinks, drugs like Adderall or Ritalin taken repeatedly over time will reduce the level of satisfaction and joy that you get from activities you engage in while under their influence.

1:20:03 Caffeine's Effect on Dopamine

Overview: In this section, the speaker talks about caffeine's effect on dopamine levels.

Caffeine could be good for your dopamine system because it upregulates D2, D3 receptors making whatever dopamine is released by that activity more accessible or functional within the biochemistry and pathways of your brain and body.

1:21:42 Dopamine and Motivation

Overview: Ingesting caffeine can increase the density and efficacy of dopamine receptors, leading to an increase in motivation, focus, and drive. However, chronically trying to spike your dopamine levels can undermine your motivation and focus in the long run. Yerba mate is a good source of caffeine that also has neuroprotective properties for dopaminergic neurons.

People who are always super motivated and driven may be undermining their ability to stay motivated by constantly engaging in activities that spike their dopamine levels.
Intermittent spiking of dopamine is the way to go for enhancing motivation, focus, and drive.
Caffeine is somewhat of an exception among other dopamine-increasing activities because it can increase the density and efficacy of dopamine receptors.
Yerba mate contains caffeine, antioxidants, and GLP-1 which is favorable for managing blood sugar levels.
Yerba mate has been shown to be neuroprotective specifically for dopaminergic neurons in both the movement-related pathway and the motivation pathway.
Caffeine can be particularly dangerous when combined with MDMA (ecstasy) as it increases the toxicity of MDMA receptors.

1:24:31 Caffeine and MDMA

Overview: Caffeine has been shown to increase the toxicity of MDMA receptors.

MDMA is under investigation for its potential to treat trauma and depression but is still illegal in the United States.
Whether or not MDMA is neurotoxic has been controversial but most data suggest that it might not be.
One study claiming that MDMA was neurotoxic was retracted because they had mistakenly used methamphetamine instead which is known to be neurotoxic.
Caffeine has been shown to increase the toxicity of MDMA receptors.

1:25:54 Caffeine, Amphetamine, and Cocaine's Effects on Dopamine

Overview: This section discusses how caffeine can upregulate receptors and lead to more toxicity of MDMA. It also explains how amphetamine and cocaine can cause long-term problems with the dopaminergic pathways by limiting neuroplasticity.

Caffeine ingestion can be beneficial in one context but dangerous in another.
Amphetamine and cocaine greatly increase dopamine levels and can cause long-term problems with the dopaminergic pathways.
A study published in the National Academy of Sciences showed that ingesting amphetamine and cocaine limits plasticity and learning subsequent to taking them.
Neuroplasticity is the brain's ability to change in response to experience, which is the basis of learning and memory.
The use of drugs like Adderall, Ritalin, modafinil, and armodafinil leads to very large increases in dopamine that could provide the same sort of blockade of neuroplasticity that cocaine and amphetamine do.
Spiking one's dopamine too much on a regular basis without a valid clinical need for doing so should be avoided.

1:28:46 Acknowledging Dopamine's Positive Effects

Overview: This section acknowledges that dopamine feels great but emphasizes the importance of understanding how it works in our brains so we can continue to engage in dopamine-evoking activities safely.

Being motivated, craving things, and being in pursuit feel wonderful because they evoke dopamine.
There is a place for ingesting things that can increase dopamine provided they are safe for us in the short and long-term.
There are activities we can do that will give us healthy sustained increases in dopamine both when peaks happen as well as maintaining or even increasing our baseline levels of dopamine.
Cold exposure has become a trend towards more people.

1:30:02 Cold Water Therapy and Neuromodulators

Overview: This section discusses the benefits of cold water therapy on neuromodulator systems, including dopamine. It also highlights the importance of approaching this practice with caution due to the risk of cold water shock.

Vincent Priessnitz popularized and formalized cold water therapies in the 1920s.
Cold water exposure can boost the immune system and increase feelings of wellbeing.
Getting into very cold water (30°F or lower) can put someone into a state of cold water shock, which can be fatal.
Most people can benefit from getting into 60°F or 50°F water, depending on their level of acclimation and comfort.
The temperature of water one can tolerate depends on how cold-water adapted they are and how familiar they are with the experience.
Getting into cold water always evokes a release of epinephrine, causing physical sensations such as quickening breath, widening eyes, feeling unable to catch breath, and even some physical pain at the level of skin.
A study published in the European Journal of Applied Physiology found that upon getting into cold water, adrenaline and noradrenaline levels increased immediately and significantly. Dopamine levels started to rise slowly but continued to reach levels as high as 2.5 times above baseline over time (up to three hours).
The sustained rise in dopamine from a cold-water exposure is comparable to what one sees from cocaine but without a rise-and-crash effect.

1:32:06 Human Physiological Responses to Immersion into Water

Overview: This section discusses a study that looked at human physiological responses when exposed to warm, moderately cold or very cold water.

A study published in the European Journal of Applied Physiology looked at people's concentrations of epinephrine, norepinephrine, dopamine when exposed to different temperatures (32°C/20°C/14°C).
Upon getting into cold water, adrenaline and noradrenaline levels increased immediately and significantly for all participants.
Dopamine levels started rising slowly but continued up to three hours after immersion in very-cold-water conditions (14°C), reaching levels as high as 2.5 times above baseline.
The increase in dopamine from a cold-water exposure was comparable to what one sees from cocaine but without a rise-and-crash effect.

1:34:08 Release of Stress Hormones in Cold Water Exposure

Overview: In this section, the speaker discusses a study that looked at the release of stress hormones like cortisol and epinephrine during long exposure to cold water.

The study found an increase in cortisol levels, especially at the coldest temperature.
However, the increase was transient and eventually subsided.
There are two approaches to remaining in cold water when it's uncomfortable: relaxing oneself or ramping up internal autonomic arousal.
Some people distract themselves from discomfort by reciting the alphabet or doing something else.

1:35:18 Warning Against Long Exposure to Cold Water

Overview: The speaker warns against getting into cold water that is so cold it will make your temperature drop and make you hyperthermic for an hour.

This could be dangerous for many people as they might have a hard time reheating, leading to hypothermia.
It's well-established that getting into cold water can evoke norepinephrine release immediately and dopamine release over a longer period of time.

1:36:02 Benefits of Cold Water Exposure

Overview: The speaker discusses how cold water exposure can raise the baseline of dopamine for substantial periods of time, leading to heightened calmness and focus after getting out of the water.

Cold water exposure is a potent stimulus for shifting the entire milieu of our brain and body, allowing many people to feel much better for a substantial period of time after getting out.
Some people do this every day while others do it three days a week or every once in a while.
Once you become cold water adapted, it no longer evokes the same release as before.

1:37:43 The Potency of Stimulus

Overview: This section discusses the potency of a stimulus and how it affects our dopamine system.

A rise in baseline by 250% is equivalent to two and a half times the rise in baseline caused by cocaine.
It is important to approach this information with caution and safety in mind.

1:37:57 Positive and Negative Aspects of Rewards

Overview: This section talks about the positive and negative aspects of rewards for our behavior, as well as a protocol to achieve a better relationship with our activities and dopamine system.

Rewards can be monetary, social, or any kind.
Dopamine relates to our perception of time.
Working hard for the sake of a reward that comes afterward can make hard work more challenging and make us less likely to lean into hard work in the future.
Intrinsic reinforcement (doing something because we enjoy it) versus extrinsic reinforcement (doing something for a reward).
When we receive rewards, we tend to associate less pleasure with the actual activity itself that evoked the reward.
Dopamine controls our perception of time.
Engaging in an activity because of the reward extends the time bin over which we perceive that experience.

1:39:04 Experiment on Rewards

Overview: This section discusses an experiment done at Stanford on children who liked drawing.

Children who liked drawing were given gold stars as rewards for their drawings.
After they stopped receiving gold stars, these children had a lower tendency to draw on their own than before they received any rewards.
No one was telling them to draw; they intrinsically enjoyed it.

1:40:06 Perception of Time

Overview: This section explains how dopamine affects our perception of time when engaging in activities for rewards.

When we engage in an activity because of an expected reward, we extend the time bin over which we perceive that experience.
Because the reward comes at the end, we start dissociating neural circuits for dopamine reward that would have normally been active during the activity.

1:41:36 The Antithesis of Growth Mindset

Overview: In this section, the speaker discusses the concept of growth mindset and how it relates to effort and performance.

Growth mindset is the principle of striving to be better and focusing on the effort itself.
People with growth mindsets tend to perform well because they are focused on the process rather than just the end goal.
Cultivating a growth mindset involves learning to access rewards from effort, which can be challenging because it requires engaging the prefrontal component of the mesolimbic circuit.

1:42:23 Accessing Rewards from Effort

Overview: In this section, the speaker explains how accessing rewards from effort can lead to increased dopamine release and improved performance.

Accessing rewards from effort involves telling yourself that the effort is great and pleasureful, even if it may be physically painful or mentally challenging.
Over time, you can start to associate a dopamine release with friction and challenge.
Dopamine has properties that increase energy levels in both body and mind, as well as improving focus by converting into epinephrine.
Focusing only on the end goal undermines your ability to generate rewarding circuits while in effort. This makes future efforts more difficult because you need more external sources of motivation like coffee or energy drinks.
To improve performance in hard endeavors, it's important not to layer in other sources of dopamine but rather subjectively attach feelings of friction and effort to an internally generated reward system.

1:45:35 The Pleasure of Effort

Overview: In this section, the speaker discusses how effort can evoke dopamine release and increase pleasure. He also talks about the importance of attaching dopamine to effort itself rather than a reward that comes after it.

Effort can evoke an increase in dopamine release later, leading to an increase in baseline dopamine.
Attaching pleasure to effort is different from thinking about the reward that comes at the end.
David Goggins is an example of someone who has made a career out of turning effort into a reward.
Throughout evolutionary history, people have revered those who were willing to put in effort.
Accessing pleasure from effort is accessible to all of us.
To prevent interference with getting dopamine release from effort itself, don't spike dopamine prior or after engaging in effort.
Intermittent fasting is an example of learning to attach dopamine to effort and strain as opposed to a process or reward that naturally evokes dopamine release.
When we ingest food or when we are about to ingest food, our dopamine levels go up.
Fasting increases our perception of dopamine.

1:49:15 Fasting and Dopamine Release

Overview: In this section, the speaker discusses how fasting affects our dopaminergic circuitry and why some people find it easier not to eat at all than eat smaller portions.

Typically, when we eat we get dopamine release, especially when we eat after being very hungry.
Deprivation states increase the way dopaminergic circuits work and heighten our perception of dopamine.

1:49:44 The Rewarding Properties of Fasting

Overview: This section discusses how fasting can evoke dopamine release and the rewarding properties of deprivation.

Fasting evokes more dopamine release when you finally eat because of an upregulation of receptors for dopamine.
The longer you restrict yourself from a rewarding behavior, the greater the dopamine experience when it is finally released.
It's important to focus on the dopamine that can be consciously evoked from deprivation, strain, and effort rather than too much reward at the end.
Many people who practice fasting say that their state of mind is clearer and they start to enjoy the period of fasting. Some even push out their eating window or skip entire days of eating to get deeper into that state of mind where they create dopamine release from deprivation, not from food reward itself.
Deliberately restricting food has been practiced for centuries in different cultures and religions to increase both the rewarding properties of food itself and deprivation.
Knowledge about the benefits of fasting serves as reinforcing dopamine-amplifying aspects to fasting. People enhance the rewarding properties by telling themselves things like "my blood lipid profiles are probably improving" or "I'm going to live longer."
Forebrain knowledge can shape circuits involved in generating rewards for primitive behaviors like eating or sex. Dopamine is attached not only to primitive behaviors but also to things we decide are good for us and important for us, such as exercise or studying.
Hearing something that reinforces one's prior beliefs can evoke dopamine release because the pathway is vulnerable to subjective interpretation.

1:53:34 Dopamine and Perception

Overview: This section discusses how dopamine and our perception of things can shape the way we experience pleasure. Studies on sugar appetite and sense of pleasure from sweet things show that if you ingest something you like, but then ingest something even sweeter or more savory, when you go back to the food you ate previously, you won't like it as much. This shift in perception can be blocked by blocking the shift in dopamine.

Dopamine release peaks and valleys affect our experience of anything.
Big dopamine release makes it more challenging to experience more big dopamine release.
Staying in a dynamic range is important for everyone.
Highly palatable foods make bland foods taste less good at least for a while.
Short periods of not consuming highly palatable foods can make whole foods taste delicious again.
Dopamine establishes value based on what was experienced in the days and minutes before.

1:55:49 Pornography and Dopamine

Overview: This section explains why pornography can negatively shape real-world romantic and sexual interactions due to its intensity evoking a lot of dopamine release. Any activity that evokes a lot of dopamine release will make it harder to achieve the same level through subsequent interactions.

The discussion about pornography is happening now, but this isn't about passing judgment on whether people like or don't like pornography.
Any activity that evokes a lot of dopamine release will make it harder to achieve the same level through subsequent interactions.
Many people who regularly indulge in pornography experience challenges in real-world romantic interactions.

1:57:02 Wellbutrin and Bupropion

Overview: This section discusses the drug Wellbutrin, also known as bupropion, which increases dopamine and norepinephrine. It was developed as an alternative treatment for depression because some people who take selective serotonin reuptake inhibitors (SSRI), which increase serotonin, suffer from serotonin-related side effects.

Wellbutrin avoids sexual side effects caused by SSRIs.
It can blunt appetite due to increased norepinephrine and dopamine levels.
Increases levels of motivation and craving but can create a state of elevated alertness that can sometimes get in the way of healthy eating.
Can increase anxiety due to the stimulating effect of dopamine and norepinephrine.

1:58:02 Dosage and Relief

Overview: In this section, it is mentioned that Wellbutrin has provided relief for many people suffering from depression who had trouble with SSRIs. It is also useful for treating smoking addiction. However, one must work with their clinician or psychiatrist to find the correct dosage.

Many people have gained terrific relief from depression using Wellbutrin.
Useful for treating smoking addiction.
One must work with their clinician or psychiatrist to find the correct dosage.

1:58:39 Supplements

Overview: This section talks about supplements that increase baseline levels of dopamine without taking any prescription pharmaceutical compounds. The two most common ones are Macuna Pruriens and l-DOPA.

Macuna Pruriens is sold over-the-counter in the United States.
It is a precursor to dopamine, meaning if you take it, you will experience very large increases in dopamine.
Those increases are transient and very intense.
Macuna Pruriens can reduce symptoms of Parkinson's disease much like l-DOPA does.
It can reduce prolactin hormone involved in milk letdown in women and setting refractory period after ejaculation in males.
Sperm concentration and quality are greatly increased by Macuna Pruriens.

2:00:35 Macuna Pruriens and Sperm Count

Overview: Four studies show that Macuna Pruriens can increase sperm count, quality, and motility. It may be a good choice for those seeking to conceive children.

2:00:50 Dopamine Increase and Crash

Overview: Consuming substances that increase dopamine levels can lead to a crash or reduction in baseline dopamine levels. Many people turn to L-tyrosine as an over-the-counter option.

2:01:41 L-Tyrosine as a Dopamine Stimulus

Overview: L-tyrosine is an amino acid precursor to l-DOPA, which lies further up the dopamine synthesis pathway. It is commonly taken in capsule or powder form and can stimulate dopamine production within 30-45 minutes of ingestion.

2:02:37 Specificity of Effect with L-Tyrosine

Overview: A study published in the Journal of Clinical Endocrinology and Metabolism showed that ingestion of L-tyrosine increased circulating dopamine levels within 45 minutes but had short-lasting effects. Ingestion of tryptophan did not increase dopamine levels, showing specificity of effect.

Note: Increasing dopamine levels through Macuna Pruriens or L-tyrosine may not be suitable for individuals with pre-existing dopaminergic conditions such as schizophrenia or bipolar disorder. Expect an elevated state after consumption, which may be agitating for some individuals.

2:04:30 Using Macuna Pruriens and L-tyrosine for dopamine

Overview: In this section, the speaker discusses his personal experience with using Macuna Pruriens and L-tyrosine to enhance focus and motivation by activating dopamine circuits. However, he mentions that he is not a fan of using Macuna Pruriens due to its intense crash afterwards. He also emphasizes that he only uses L-tyrosine occasionally to avoid relying on exogenous substances.

The intensity of the crash after using Macuna Pruriens depends on one's biology and dopamine baseline.
The speaker personally does not use Macuna Pruriens due to its intense crash.
The speaker occasionally uses L-tyrosine for enhancing focus and motivation but avoids relying on it regularly.
The speaker does not want to experience the drop in dopamine that inevitably occurs after taking exogenous substances.

2:05:18 Melatonin's impact on dopamine levels

Overview: In this section, the speaker talks about how melatonin can reduce baseline dopamine levels. He cites a study that found a statistically significant decrease in dopamine 60 minutes after melatonin administration. He advises avoiding exogenous melatonin if possible to maintain healthy levels of dopamine.

Melatonin can reduce baseline dopamine levels.
A study found a statistically significant decrease in dopamine 60 minutes after melatonin administration.
Avoiding exogenous melatonin if possible can help maintain healthy levels of dopamine.

2:07:02 Phenethylamine (PEA) as a natural source of increased synaptic levels of dopamine

Overview: In this section, the speaker discusses phenethylamine (PEA), which is found in various foods such as chocolate and can increase synaptic levels of dopamine. He personally takes PEA from time to time as a focus and work aid for mental work or training. He advises checking with a doctor before taking PEA or any other substance.

PEA is found in various foods such as chocolate and can increase synaptic levels of dopamine.
The speaker personally takes PEA from time to time for mental work or training.
Taking PEA leads to a sharp but very transient increase in dopamine that lasts about 30 to 45 minutes.
Checking with a doctor before taking PEA or any other substance is advised.

2:08:23 Nootropics and Dopamine

Overview: This section discusses the popularity of using nootropics to increase dopamine levels, specifically mentioning huperzine A as a compound that can increase acetylcholine transmission and somehow lead to increases in dopamine in the medial prefrontal cortex and hippocampus. The speaker also mentions L-tyrosine, PEA phenethylamine, and Alpha-GPC as non-prescription alternatives to drugs like Adderall, Ritalin, modafinil, and armodafinil.

Huperzine A is gaining popularity for increasing dopamine.
It is a nootropic that can increase acetylcholine transmission.
Huperzine A leads to increases in dopamine in the medial prefrontal cortex and hippocampus by way of interactions between the cholinergic system and dopaminergic system.
L-tyrosine, PEA phenethylamine, and Alpha-GPC are non-prescription alternatives to drugs like Adderall, Ritalin, modafinil, and armodafinil.

2:15:35 Quality of Supplements

Overview: In this section, Dr. Huberman talks about the importance of ensuring that the ingredients listed on supplement labels match what is actually in the bottle. He mentions that Thorne is a company that has high levels of stringency with respect to quality and how much of each supplement they put in their products.

Thorne has strict standards for quality control.
Thorne ensures that the quantity of ingredients listed on supplement labels matches what's actually in the bottles.
To see the supplements that Dr. Huberman takes, visit www.T-H-O-R-N-E.com/u/huberman.
By navigating into the Thorne site through that portal, you can get 20% off any of their supplements.
Follow Huberman Lab on Instagram and Twitter for more neuroscience tools and information.

2:16:25 Conclusion

Overview: In this final section, Dr. Huberman thanks viewers for their interest in science.

Thank you for your interest in science!

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