Transcription
Dopamine hacking, dopamine stacking, dopamine fasting. You see it all over the internet. But today, I'm going to set the record straight about dopamine. You're probably seeing me really irritated today, and you're probably right. But stay with me till the end of the video, and I'm sure you'll understand why. Because frankly, what we see about dopamine can be considered as total BS. It's oversimplified and completely misses the point about what dopamine, as a crucial neurotransmitter, does for us as human beings. So, if you think dopamine's just about this feel-good button, you're in for a surprise. So stick around as we unravel the complexities of the brain's oldest neurotransmitter and learn how to genuinely make a difference to your life by understanding the science of dopamine.
So, in this video, I'm going to cover six points. First, the evolution of dopamine. Next, the discovery of the role of dopamine in medicine. Third, dopamine misunderstandings and the true role of dopamine. Fourth, the risks of an excessive focus on dopamine optimization. Fifth, how to improve your well-being through a scientific understanding of dopamine. And a sneak peek into narcissism and dopamine. Do individuals with narcissism have low or high levels of dopamine? Find out the answer at the end.
Hi everyone, I'm Dr. Seil Reg, consultant psychiatrist, and welcome to Psychiatry Simplified, the channel where we cover psychiatry, neuroscience, and all aspects related to mental health. So, if that's your thing, don't forget to hit the subscribe button to stay in touch with all our future videos.
For over two decades, my work in psychiatry has given me unique insights into the neurotransmitter landscape of the human brain. As a clinician, I've got access and have been trained in utilizing medications that have the potential to modulate these crucial neurotransmitters: serotonin, glutamate, Gaba, dopamine, noradrenaline, etc. I'm able to use agents, and most importantly, I'm able to see their effects on human behavior, cognition, and activity. And this is the most important point because just talking about dopamine as a molecule independent from the entire modulated system just completely misses the point.
You see, as a clinician, I see presentations where there is significant psychomotor retardation, slowing of movement, slowing of cognition. And I can use a range of agents: dopamine, noradrenergic potentiators, agents that may act directly on dopamine receptors, agents that might simply increase levels of dopamine in the synaptic cleft, versus utilizing other neurotransmitters to indirectly modulate dopamine. And through these pathways, I can make a difference to this patient, improving their cognition and activity.
You see, psychopharmacology is an art of modulation, and we're able to see it in practice. For example, when I prescribe a certain dose of an agent, a dopamine potentiator, for example, I can predict to a certain extent. It's not an exact science, but it's good enough to understand that there will be an X amount of reduction of certain symptomatology or an X amount of improvement of a certain symptomatology. And that's what leads to my dose adjustment.
So, to simply hear someone talk about 10 ways of increasing dopamine, you can see why that really riles me up. Because take, for example, in Parkinson's disease, where there is significant dopamine degeneration. Levodopa, a precursor to dopamine, potentiates dopamine neurotransmission, that improves activity. However, at the same time, we know levodopa can also activate impulse dysregulation disorders, such as pathological gambling or sexual disinhibition. That tells us that the dopamine system is all about modulation.
Increasing dopamine in the brain is not the same as increasing blood glucose through a carbohydrate meal or a sugary drink. It's really not the same. You see, while blood glucose levels can be raised uniformly throughout the bloodstream by consuming these sugary drinks, for example, through gluconeogenesis, dopamine levels are different. Dopamine levels are regulated a lot more intricately in certain brain regions, and that's important because excess dopamine increase in certain regions is actually harmful.
You see, dopamine production, release, and receptor activation occurs in distinct neural pathways. There are specific receptors, and there are specific neurotransmitters that increase or decrease dopaminergic potentiation. So, dopamine is linked to a range of other neurotransmitters. For example, pathways such as the mesolimbic pathway or the nigrostriatal pathway. These are responsible for reward. These are also responsible for movement. So, interventions to boost dopamine, so to say, do not uniformly increase dopamine across the brain. So, exercise, diet, lifestyle, therapy, medication, etc. What it does is it enhances dopaminergic activation in relevant brain areas. This selectivity is crucial for maintaining homeostasis and to prevent the significant dysregulation of dopaminergic pathways that are part of a range of psychiatric disorders such as schizophrenia, Parkinson's disease, bipolarity, or severe melancholic depression.
So, with that rant out of the way, let's journey back in time where we explore one of nature's most fascinating evolutionary tales: how a simple molecule, dopamine, helped shape the complex brains of today's vertebrates. Imagine Earth hundreds of millions of years ago, teeming with life, beginning to explore the open spaces. Here, dopamine made its first appearance approximately 600 million years ago, and its main function at that point in all multicellular organisms was motility. These were multicellular organisms in search of food, reproduction, and survival.
But the plot thickens, particularly as we move up the evolutionary ladder. Enter the basal ganglia, a group of structures in the brain of vertebrates, including us humans, that control movement but are connected to the cognitive parts of the brain. The basal ganglia structures, you might have heard of some of them, such as the caudate, putamen, globus pallidus. These are responsible for movement, but importantly, they connect to the cognitive parts of the brain. And therefore, as we moved up the evolutionary ladder, the saying "to think is to move" encapsulates this perfectly.
You see, unlike simpler organisms where there was one excitatory dopaminergic pathway, in vertebrates, we developed both an excitatory and an inhibitory pathway through the development of the prefrontal cortex. Now, these two pathways, known as the direct and the indirect pathways, revolutionized how vertebrates, including us humans, interacted with their environment. So, for example, whilst the direct pathway helps us initiate movements, the indirect pathway, the inhibitory pathway, helps us refine and select movements that are appropriate and adaptive to the situation. So, what we've got to remember here, the way we humans function is really based on an optimal balance between the direct and the indirect dopaminergic pathway. You see, dopamine comprises 80% of the catecholamine content in the brain, making it one of the oldest neurotransmitters.
Now that we've seen how dopamine evolved, let's look at how dopamine was discovered as an important molecule in the field of medicine. Dopamine was isolated in 1910 by researchers George Barger and James Irwin. Initially, it was simply thought to be a precursor to norepinephrine, also known as noradrenaline, and therefore not much importance was given. Now, it wasn't until the 1950s that Kathleen Montagu discovered that dopamine acted independently in the brain. Now, this set the stage for Arvid Carlsson, who demonstrated dopamine's role as a neurotransmitter essential for initiating voluntary movement. His groundbreaking work, which involved reversing induced paralysis in rabbits using levodopa, the same medication that we use in Parkinson's nowadays, shifted dopamine from obscurity to a molecule vital to basic existence. This discovery was pivotal, leading to effective treatments for Parkinson's disease and earning Carlsson a Nobel Prize.
Now, fast forward to today, and dopamine is branded as the pleasure chemical or reward molecule, with a misunderstanding of what reward actually means. Social media and some corners of the health industry advocate for dopamine detox or fasting, suggesting you can somehow reset your brain's dopamine systems to increase happiness. But dopamine's role is far more complex, but at the same time, really fundamental. It's involved in a range of functions: motor control, learning, cognitive functions such as executive function, pain, sleep, emotional appraisal, impulse control, etc. Essentially, you can see what it helps us do is to be adaptive in life.
Dopamine interacts with five distinct receptor types: D1 to D5. So, there are two broad families: the D1 family and the D2 family. The important thing here is that dopamine is modulated by a range of neurotransmitters. Have a look at this image here, and you can see that the serotonergic receptors, the endocannabinoid receptors, Gaba, glutamate, muscarinic, and nicotinic receptors all interact with each other, having excitatory inhibitory effects, and all roads ultimately lead to dopamine. So, as a clinician, I can use a range of strategies, agents, for example, acting on the endocannabinoid pathway or the serotonergic pathway or the Gaba or glutamate pathway to modulate dopamine. The important thing here is that the utilization of psychopharmacology isn't just about increasing dopamine; it is about modulating neurotransmitters using psychopharmacological agents in the best way we can to improve the individual's functioning. And these functions involve cognition, activity, emotion, perception, and sleep.
So, coming back to dopamine, dopamine is synthesized in the neurons from the amino acid tyrosine, and iron acts as a really important co-factor to convert tyrosine into levodopa. Levodopa is the precursor of dopamine, and dopamine then gets broken down through enzymes MAO-A and MAO-B. And dopamine itself is a precursor to noradrenaline in the presynaptic neuron. Dopamine is packaged into vesicles by VMAT2, the vesicular monoamine transporter 2, and from here, it's sent out from the presynaptic neuron into the synaptic cleft. Once it's released into the extracellular space or the synaptic cleft, it then goes and acts on the postsynaptic neuron. Depending on which receptors it acts on, it has a range of physiological functions. So, for example, broadly, the D1 receptor family is considered excitatory, D2 receptor family is considered inhibitory.
You see, the presynaptic neuron, the synaptic cleft, and the postsynaptic end have to function within a homeostatic paradigm. And what I mean by that is an optimal balance. So, if there's excess dopamine in the synaptic cleft, usually this will be taken up in the presynaptic neuron because too much dopamine in the synaptic cleft is harmful. So, essentially, there is a negative feedback to ensure that there's homeostasis and optimal balance. And at the same time, you see, the D1 receptors and D2 receptors are activated at very, very different concentrations of dopamine. And you can see there's a reason for this because the role of the D1 receptors is different from the D2 receptors, and we'll cover that in just a bit.
So, D2 receptors are considered high-affinity receptors. They are activated very, very easily by dopamine. The D2 receptor affinity is almost 100 times more than the affinity of the D1 receptors to dopamine. The D1 receptors require very high levels of extracellular synaptic cleft dopamine to be activated. So, now, when you think about these intricacies and complexity, it's almost comedic that some self-proclaimed wellness gurus or health influencers oversimplify such a complex system to simply say you can control or manipulate these delicate neurochemical processes by going on a dopamine diet. This does not mean that exercise, adequate sunlight, a good diet are not important, but they're part of an overall lifestyle modification. But the purpose isn't about increasing dopamine; there's a lot more to it, and that's my key message here.
So, in the spirit of the message and not attacking any messengers, let's now delve deeper into the understanding of the role of dopamine as a molecule. To understand dopamine, we have to understand reward prediction errors. Reward prediction errors, or RPEs, sculpt our behaviors and guide our learnings so that we can adapt to our circumstances. Think of it as the ultimate "f around and find out," but within our brains. The more you f around, the more you're going to find out.
So, let me simplify what reward prediction errors are. Imagine you're walking through a maze, and every turn that you take is a guess, a prediction. Suddenly, you find a shortcut that you never knew existed. The outcome is a feeling of surprise. That's the essence of a reward prediction error. A surprise signal is generated, and this surprise signal is generated because of an unexpected reward. What I want to highlight here is the word "reward" is about learning. You have discovered something different that's going to save time, something that is adaptive. This mismatch between what you predicted versus the outcome or the surprise that you receive kicks your brain into high gear. This is where dopamine steps in. There is a spike in dopamine release, and the spike is necessary because one, the increase in extracellular levels of dopamine activates the D1 receptor. Remember, the D1 receptor was the low-affinity receptor; it requires higher levels to be activated. And the reason why D1 receptors are so important, they're predominantly situated in the prefrontal cortex, is for learning. Because the D1 receptors are now responsible for you to remember this shortcut.
You see, you do not need repeated spikes of phasic dopamine to learn this. The surprise signal occurred, that this would be consolidated as part of your learning through reinforcement. Sure, you might need to revisit it a few more times. However, each time, you don't need significant phasic dopamine because it will move into the habit part of your brain. And by shifting this into the habit part of your brain, the prefrontal cortex is now freed up for you to discover newer areas of learning or newer surprises. So, to summarize, what dopamine does is it helps you learn. It helps you learn through the generation of surprise signals.
Similarly, if you were to encounter an aversive situation, the dopamine neurons reduced their firing. This reduction of firing results in decreased motivation and helps you remember that this particular outcome is not necessarily a satisfactory outcome, and therefore, you search for other ways to solve that particular problem. A more extreme example is not touching a hot stove after you've burnt your finger. You see, every reward prediction error that's minimized is a lesson learned because those lessons have been shifted to the habit part of your brain. This means that you now have the cognitive capacity for newer learning, newer surprises, and newer understandings. Dopamine, through the reward prediction errors, acts as a navigational compass through which we can manage uncertainty, the unpredictability that we will encounter in life, and it ensures that our future predictions align as closely with the best possible outcomes.
Why does this matter? It matters because life thrives on unpredictability. Environments rich in novelty and exploration boost dopamine-driven learning, making us more flexible and more adaptable. This is why we crave variety, and routines sometimes make us feel dull. But the key here is to remember that we need an optimal balance between routines and variety. If there is too much novelty and it results in repeated phasic spikes of dopamine, this actually can impede learning because we're not meant to function on repeated phasic spikes of dopamine. So, really, as we go through life, our brain is constantly adjusting to the circumstances that we encounter. And here, dopamine plays an important role through the modulation of the direct and the indirect pathways, the modulation of the different receptors, the D1 versus D2, so that you as a human being can operate actively. So, if there's one thing to remember here, it's to remember the word "balance." It's about an optimal D1 versus D2 balance or optimal direct pathway versus indirect pathway.
Now, knowing this, what are the actual risks of this focus on dopamine optimization? The belief that increasing or resetting dopamine is the key to happiness? Let's explore that a bit further. You see, there's no such thing as a dopamine mindset. Because in seeking for peak mental states, as many call it, there's a risk it turns us into seeking animals. And we know seeking mimics a substance-use type paradigm, an addiction paradigm. In addiction, the individual moves from liking to wanting to seeking. But seeking becomes an addiction-type phenomenon, which becomes all-consuming. And here, there's a risk it turns the quest for dopamine into a formula, a formula that does not exist.
Some try to micromanage this system with detailed regimes, chasing an optimization that ironically leads to a dopamine deficit. And let me tell you how. You see, there is a phenomenon known as the reward deficit state, and the reward deficit state involves dopamine as a prominent neurotransmitter. You remember that phasic release of dopamine is linked to unexpected rewards. So, what happens when we over-structure our life around expected rewards? What it does is it actually diminishes our exposure to the new and unexpected, the serendipitous, stifling the very surprises that nurture our brain's cognitive flexibility. So, we move from a cognitive flexibility model to cognitive rigidity. And in this case, the rigidity may be linked to optimization. Our routines, our behaviors, our cognitions are all related to the single paradigm of optimization.
Now, this is seen across the spectrum. For some individuals, this can be extreme. What the point I'm trying to make is the very belief that one can increase dopamine levels through a rigid optimization schedule is actually paradoxical because the very rigidity is associated with a dopamine deficit state, also known as the reward deficit state. Now, the reward deficit state can be associated with a range of psychiatric disorders. At the extreme end, the reward deficit state can be induced through excessive scrutiny or high levels of perfectionism, or in some cases, the perfectionism or the excessive scrutiny can be a compensatory behavior in the context of this reward deficit state. Perfectionistic traits, a cognitive style characterized by stringent self-standards, high levels of criticality, often self-doubt, can increase the risk of a depressive syndrome, which is really part of a reward deficit state.
So, understanding this paradox. In a world buzzing with dopamine diets and quick fixes, it's time to ask: how do we truly incorporate the scientific understanding of dopamine in our everyday lives? The answer is really simple: just be. Now, it's probably not the most eloquent way of communicating something philosophical, but to just be is to engage with life as it unfolds, staying curious and being open to new experiences because that's where the phasic dopamine increase occurs in the context of the unexpected, the surprises.
This principle is actually not new. It's etched in philosophies such as the Japanese concept of Ikigai. I've actually covered this in this video here. It encourages us to find joy not just in personal gains but also in thinking about how we can contribute to society. Similarly, in Indian philosophy, the words Karma and Artha, which means actions and purpose, ask us to focus on meaningful goals rather than immediate rewards. The shift from immediate gratification to delayed gratification, in fact, the shift from immediate gratification to delayed gratification is part of the treatment paradigm in ADHD, and I've covered it in this video here. So, you can see how all of this is interlaced.
The philosophy of imperfection as an important part of life is encapsulated in the Japanese philosophy of Wabi-sabi, finding beauty in imperfection. We know Kintsugi, where broken pottery is repaired with gold, highlighting flaws as unique attributes rather than defects. These concepts remind us that true perfection involves embracing imperfections. In a way, in fact, a similar saying exists in Sanskrit as well. The saying, it basically means that to achieve something or to accomplish something, incompleteness is essential.
So, what's the key takeaway? How do you incorporate dopamine's role in your life? The answer: embrace life's spontaneity. Allow the unexpected to be your teacher. Modulate the D1 discovery pathway and the D2 endurance pathway by having a balance in your life between novelty and routines. Nurturing both immediate gratification at times versus delayed gratification at times. So, to summarize, the key to harnessing dopamine lies not in supplements or detoxes, but rather than embracing a life full of curiosity and openness to new experiences. Dopamine, as a molecule, thrives on unpredictability and learning, attributes that are naturally rewarding and self-reinforcing. We aren't meant to experience pleasure all the time. We aren't meant to experience repeated phasic dopamine bursts that mimic stimulus-bound responses that occur in addiction behaviors or compulsive behaviors.
Remember that dopamine is a molecule evolved to help us share and contribute to the world. In fact, narcissism, particularly in the pathological form, is hypothesized to be associated with the reward deficit state that I talked about. This dopamine deficit state is compensated not through drugs, although drugs can be present, but through an addiction to self-esteem mirroring substance dependence. But here, the drug is self-validation and approval. I've touched on it in this video, but we will delve deeper into this concept another time.
So, I hope this video has given you an understanding of the complexity of this amazing molecule, dopamine. But I hope that this video has also given you some really important tips to enhance your well-being. If you like the video, don't forget to leave us a like and of course, subscribe to our channel. It helps us a lot. Don't forget to leave your comments and let us know what other videos you'd like. I look forward to seeing you in another video soon. Until then, stay curious. Bye-bye.