Why Depression Is A Chemical Imbalance: Lessons From MDMA, Self-experiments, Bipolar Disorder
Mental health is the strongest individual predictor of life satisfaction. The mind is all we have. Given this, mental illness can take away our lives. In this article, I will make the case that mental illness is strongly connected to brain circuits and brain metabolism, and consequently depression is to a major degree a “chemical imbalance”. However, the connection is not as straightforward as you might think.
At the age of 23, I started to replace all of my major hormones. Since then, I have learned quite a lot about how changes in biochemical parameters affect your wellbeing, and as a result, your life. If you change biochemical parameters, over time, your life and happiness will evolve in a way that reflects these changes. For my own personal story: How Hormones Destroyed And Saved My Life -From The Brink Of Suicide To Bliss. Most of my other articles are about hormones. However, this article is different. It is more about neurobiochemistry in general, of which hormones are just a part.
About the author: Everything in this article represents solely the personal opinion of a young fictional medical doctor, who wrote a number of articles to counter the massive amount of misinformation he has come across. By definition, an opinion need not be based on facts or truth. Nothing must be interpreted as a statement of advice by an expert. Everything is for informational and entertainment purposes only. The author of this article does not endorse the use of any supplements, pharmaceutical drugs, or hormones without a doctor’s supervision. If you have any queries related to health, diagnosis, or treatment, always consult with a licensed medical professional.
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The mind is what the brain does.
In my very early days of hormone optimization, I was on the fence. I needed time to think. Time to ponder why my life was falling apart and time to think about whether I want to keep replacing my hormones for life.
To do so, I had locked myself up in a monastery. After some sleepless nights of back and forth, and invigorated by the stimulating effects of the active thyroid hormone that I had started only a few weeks ago, I decided that I wanted to come off everything and just be “normal” like everyone else. I quit everything. Cold turkey.
Bad idea.
“Should I or should I not replace my hormones for life? Will I even be able to? What if an apocalypse happens and I lose access to all the meds? What if I have severe side effects down the road? Will I wreck my health? Am I fake? Am I becoming a robot? What will my wife say one day? My kids? Will I even be able to have kids? Will I even find a wife in the first place?… Am I even lovable?”
Panic attack.
At that moment, all rationality was gone. I was completely carried away by a crescendo of ever-more destructive thoughts and emotions, both amplifying each other. Words are useless to describe the kind and intensity of the anxiety I was feeling at that moment.
I knew that there was nothing I could do, no way my life would ever get better.
The window was open. In these moments of hopelessness and helplessness, people do stupid shit. One brief moment is all you need…
Fortunately, a priest came to my rescue.
What I did not know at that time was this. After quitting the active thyroid hormone cold turkey, my body temperature had dropped to below 35C. To maintain core temperature, my body’s sympathetic nervous system has gone berserk. My body and brain were suddenly brimful with adrenaline.
I was led to believe that the shaking, the rapid heartbeat, the palpitations, the feeling of being choked, etc. were conjured up by my thoughts. But it was the other way around.¹
All the destructive self-doubts and grim outlooks on life were a reflection of my biochemistry. A consequence and not a cause. With such an army of adrenaline cruising around my bloodstream for “seemingly” no reason, I could not not get anxious.
Let’s go back to a few weeks before this event, the time when I started replacing my thyroid hormones properly. Back then, I was excited about life, full of energy and optimism. I felt a little “superhuman” because of how much of my biology I can control.
While just a few weeks before I was “feeling too well”, now, it was the opposite. Anxiety, depression, and even thoughts about suicide for a brief moment.
Let’s go back even further. A few months before all this, my hormones were worse than “meh”. I perceived my life to be dull and grey.
From just trying to get by (months before), to thoughts of grandeur (weeks before) to extreme self-doubt (now). Funny, because the objective content of my life situation had not changed over this time. Certainly not enough to warrant such wild swings in my state of mind.
However, one thing had changed. My neurobiochemistry. In each of these periods, neurobiochemical changes were reflected in my thoughts and outlooks on life, swinging from barren wastelands, to heaven, to hell.
I reintroduced the active thyroid hormone slowly.
As my neurobiochemistry reversed again, so did my thoughts, outlook, and thinking patterns. For a brief time, I felt a little “too well” again. I was incredibly grateful to be alive and could not relate anymore to why the heck I had so been anxious.
Even though now I knew exactly what was happening neurobiologically, I was still carried away by my underlying emotional tone. The subjective experience was too intense, visceral, and raw for me to rationally talk myself down from the euphoria. Telling myself “this is biology” was useless.
Sometimes, it does not matter what we know, but what we feel takes over.
From this (un)fortunate experience, I learned three lessons.
First, hormones (or drugs that mess with neurobiochemistry) are nothing to be played around with, especially if you do not know what you are doing. While one certainly can have a valuable learning experience, one could also do something really stupid. Something irreversible, which will leave a lasting impact on someone’s life and the life of others.
Secondly, it is impossible to imagine what it is like to suffer from a mental illness without having briefly touched the limits of the fragile condition we call sanity. If nothing else came from all this, as a prospective physician, at least now I truly understand what it means for people to have an anxiety disorder. Now, I have deep compassion especially for people with bipolar disorder, perpetually and naturally cycling between these two states – often in rapid succession. And minor versions of this cycling are experienced by half of the fertile human population, every single month.
Thirdly, we are deeply biological creatures. Our emotions, thoughts, outlooks, and thinking patterns are at the mercy of our neurobiochemistry and its changes.
While the sudden withdrawal of active thyroid hormones is certainly not generalizable, all this does beg the following question: How would my life have turned out if my brain state at the time of the panic attack had been my baseline?
Most likely, I would have developed a severe anxiety disorder quite early in my life. Likely, I would have always tried to battle my neurobiology, eventually realizing that I was powerless and stood no chance against these forces. Likely, I would have been placed on psychiatric drugs from early on -if I was lucky.
Many lives are wrecked from very early on by genetic or developmental aberrances in neurobiochemistry. Being a medical student, I knew this before. But I “knew” it in a way medical students “know”. Now though I could relate on a deeper level. Now I could feel what it actually means for someone’s subjective micro-universe. That goes far beyond any textbook knowledge or cold statistical correlations detached from any tangible reality.
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MDMA: every conscious state emerges from a brain state.
Let’s embark on a thought experiment. Imagine you live in a country where MDMA is legal and in a couple of days, you plan on taking MDMA for the first time.
Let the days before this legal experience represent your baseline in terms of how you normally feel on a daily basis, ranging anywhere from depressed to optimistic.
Finally, in eager anticipation, you lawfully pop the pill.
After around 90 minutes or so, you are coming up. You feel invincible, utter euphoria, grateful to be alive. Pure love for yourself and others. An upward shift in valence by many orders of magnitude.
As your neurobiochemistry changes, your thoughts and outlooks on life follow suit. Many of your problems disappear. It is not that you do not remember them. No, you are quite lucid and very aware of your problems. However, now -full of energy, motivation, euphoria- you view these problems through a completely different lens. You even see putative “solutions” to your problems and you are eager to tackle these in the future.
The “what is” did not change, but the “how you see it” did.
Let’s fast forward 24h. A time when many of your monoamine stores have been depleted. Your neurobiochemistry has changed again, but now in the opposite direction.
You are now depressed. You almost start to cry for seemingly no reason. You feel empty and might even ask: “What is the point?”
Welcome to Suicide Tuesday.
Whereas just hours ago your thoughts and outlooks on life were filled with euphoria and grandiosity, now they are the complete opposite. This is despite the fact that the objective information about your life has not changed at all within this short span of time. However, what has changed, is how you view and frame things.
In both instances, your views, thoughts, and outlooks on life are secondary and simply a puppet of your neurobiochemistry.
PG-13 version: If you have never taken MDMA before, think about a time when you tried to beat your addiction to caffeine. Battered by the side effects, perhaps after only a few days, you give in. Once you take that first teeny-tiny sip of coffee, the grey world suddenlty turns into color again. You are excited about life, even though just minutes ago you were semi-depressed and your outlooks were dull and grey.
Some of you will say all this does not matter because it‘s all substance-induced and thus, “artificial”. Well, while not as stark and illustrative, let’s go over some more “natural” examples.
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Sickness. Sleep. Fasting. Running. Cold shower.
Have you ever felt sad and pessimistic for seemingly no reason while being sick?
Have you ever had an exceptionally bad night of sleep and on the following day you were moody and anxious?
Has euphoria ever crept up after your first bite of food after going for a long time without eating?
Have you ever gone for an intense workout and experienced a boost in mood that lasts for many hours?
Have you ever felt like a million bucks right after a cold shower and has this also suddenly changed the way you think right after?
With all these examples, your objective life situation does not change. However, your neurobiochemistry does. And so do your thoughts and outlooks, although secondarily as a consequence of your new neurobiochemical state playing puppet with your higher, more rational mental centers.
Note: For scientific explanations about these examples, see Footnote 2.
The point I am trying to make is this — the quality of your life depends on the quality of your mind, which emerges from the brain. And every conscious state emerges from a specific brain state. In fact, the mind is what a brain does.
But what do all these sudden changes in neurobiochemistry have to do with chronic, lasting depression?
Our individual baseline neurobiochemistry goes far beyond how we are simply feeling at each moment because how we feel at each moment affects the decisions we make (and made), the things we do and do not do, the thinking patterns we developed over the years. All these then have powerful ramifications on every domain of our life and are also a major reason why our life turned out the way it did.
To better understand the chronic effects of these “chemical imbalances” the following disorder illustrates this point quite perfectly.
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Bipolar Disorder
Bipolar disorder is a condition where the afflicted person cycles between periods of mania (the “high”) and depression (the “low”).
These changes are brought about by fluctuating levels of monoamines. When monoamine levels are high, so are they. When they get low, they do too.
During their “high” period, they feel more than “well”. They are motivated. They are creative. They do. They come up with countless projects. They start companies. They sometimes do things that are irrational and stupid to the outside observer.
As their monoamines oscillate downward again, so do their energy and motivation. At this point, they are depressed, listless, and deeply regret what they were doing only a few weeks ago.
Kanye West went from running for president to breaking down sobbing like a child. Ernest Hemingway went from writing The Old Man and the Sea in one go to shooting himself in the head. Curt Cobain went from nirvana to blasting himself into the real version of it.
On a neurobiochemical basis, this is very similar to me starting supplementation with the active thyroid hormone, its cold-turkey withdrawal, and its reinstatement. It is also quite similar to MDMA vs. Suicide Tuesday – with the only major difference being that the cycles in bipolar disorder are usually of much longer duration.
Well, what does all this have to do with you?
People who suffer from bipolar disorder have a neurobiochemical state that is very inconsistent and both strongly and dynamically fluctuating.
However, most of us have a baseline neurobiochemical state that is for the most part quite constant and stable. While slight changes to this state are happening to some degree all the time (for example, whenever we get sick, whenever seasons are changing ( →SAD), whenever we make significant changes to our diet or sleep patterns, whenever we ingest any substance that influences our neurobiochemistry, if we are an ovulating female, etc.), for the most part, our baseline neurobiochemistry, and therefore our energy, mood, and motivation do not cycle much.
This state of baseline neurobiochemistry then strongly influences how we feel on a daily basis (e.g. depressed, listless, motivated, enthusiastic), which then strongly influences our actions. Both of which then, in turn, are major determinants of our outer and inner life.
Most people assume the following sequence of events:
- Conceptual changes (e.g. negative thoughts) → feeling
In reality, though, it is just as often the other way around:
- Feeling (changes in neurobiochemistry due to whatever reason) → conceptual changes (e.g. negative thoughts)
In fact, positive vs. negative thoughts, moods, and outlooks are (more) often caused by our underlying neurochemistry rather than themselves being the direct cause for us to feel good or bad.
Practical: If you want to change your mood and thoughts, focus on your body first (even if this “just” means sleep, exercise, nutrition). Why? Neurobiochemistry →mood → thoughts. If you feel lethargic and unmotivated, then it is just a matter of time until your biochemical profile is reflected in your thoughts and thinking patterns. Going for a run, eating some good food, getting a good night’s sleep, etc. are sometimes all that is needed for us to solve some of the “existential” crises we may have. At the very least, this will put us in a state of mind from which we can more calmly and objectively look at whatever problems we may have and to help us tackle whatever needs to be tackled.
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Biology, your life, and happiness
Science claims happiness to be determined to 50–80% by genetics. This has been concluded in multiple, independent studies by continuously sampling the happiness-level of monoecious twins separated at birth (to correct for any non-biological factors). This means that for the average human being, biological factors are more important than all the other factors combined.³
Note: Many of the genetic factors that have been found to be correlated to happiness levels are genes associated with monoamines and hormones, both of which are major determinants of our energy levels and mood.
However, genes’ effect on happiness is not by making someone “happy” in the same way recreational drugs make us “happy”. The effects of genes on our level of happiness are to a large extent indirect. Genes influence our biochemistry. Our biochemistry then influences not only affect our moment-to-moment well-being (the way we “feel” on a daily basis) but also our thinking patterns, the way we act, and therefore our life overall: relationships, wealth, relationships, status, profession, etc. — which all have independent effects on our happiness levels. For some data regarding this, see footnote 4.
The ripple effects of biology
Biological factors ripple through our lives the same way an earthquake ripples through the Earth’s crust.
No domain of our lives is out of biology’s purview. From energy levels, mood, health, IQ, looks, brain wiring, cognition, motivation, concentration, emotional reactions, personality traits, etc. Among other things, all these then influence the thinking patterns we have evolved over the years, the lifestyle we led, and the decisions we made, which together, over time, are reflected in every aspect of our life.
People high up in social and economic ranks, people with impressive “conventional” life success -wealth, status, relationships, in general, have above-average vitality (energy, mood, health).
Having been dealt good cards in the “genetic” lottery contributed a large share to their success in life, much more than they are likely aware. Of course, they worked hard. However, great energy, mood, health, drive, concentration, etc. allowed them to be motivated and work hard in the first place. Whatever the value they got from this, this value was reinvested daily. And compound interest is the most powerful force in the universe.
The opposite holds for people not having achieved “much” in life. If energy, mood, and health are low all the time, people are more likely to procrastinate, withdraw, sleep in, not exercise, choose the easy things. Downstream all of this, they willingly -or forcibly- settle for the mediocre (or less) quite early.
Side note: Single nucleotide polymorphisms and other gene variants associated with hypomania (the “high”) are much more common in US citizens, espescially in direct descendants of early founders. These early founders, on average, had greater levels of energy and enthusiasm compared to the people they left behind in their home country. The energy and motivation necessary to set for a brave new world. Then, they left their genetic legacy to their descendants, who have a reputation for “action” and moving things forward. These descendants then initiated one of the most dramatic rises of a nation state ever seen in history. Well, there is in part a biological reason for this.
Hormones
From all the biological factors, hormone levels are the most powerful. By far. This connection between hormones and happiness is so incredibly important that it deserves to be mentioned. (Read the section Hormones and Happiness here: How To Fix Your Hormones: The Ultimate Guide.)
How antidepressants really work
Some background
Depression is a catch-all term for countless different syndromes, all quite distinct from each other. The only common denominator between different depressions from different people is “prolonged subjective suffering”. For my personal understanding of psychiatric disorders read my short excerpt about it here.
In the same way that happiness is not just genetically determined, depression is not just a chemical imbalance. Being depressed means not liking the story you tell yourself about your life and not liking the character you play in it.
At the root of depression is this notion that there is no light at the end of the tunnel. That it will never get better (“hopelessness”) and that there is nothing you can do about it (“helplessness”).
When it comes to how this state of hopelessness and helplessness arises, one of the most important factors is the level of monoamines (dopamine, serotonin, adrenaline). Monoamines affect the way we feel. Well, this is an understatement. They mostly determine how we feel.
If we are (biologically) in a bad mood, which is first and foremost related to low levels of monoamines, our thoughts and outlooks will follow suit.
Note: Briefly, high levels of dopamine make us feel “I am motivated”, high levels of serotonin “I am calm and relaxed”, and high levels of noradrenaline “I am alert and awake”. Our setpoint and balance between these monoamines has a major effect on why we are the way we are and why our life has turned out the way it did, perhaps starting as early as the second month of pregnancy, a time when the rudimentary brain lays the groundwork for its future wiring. Unless someone is using a neuropharmaceutical drug on a daily basis, the main factor that determines the individual baseline level of any of these monoamines at any given point, is genetic factors and hormones. While genetics is more or less constant, hormones are not. As our hormones change, so do our monoamines (e.g. during the female cycle).
Let’s look at the examples from above:
- As stupid past-me quit the active thyroid hormone, dopamine and serotonin took a nosedive, whereas noradrenaline soared.
- With the lawful use of MDMA, dopamine and noradrenaline accumulate in the synaptic cleft, while serotonin is released in addition.
- For people with bipolar disorder, monoamines (esp. dopamine) fluctuate from high to low levels.
In each of these instances, the changes in how the person feels and thinks (and acts) reflect the changes in monoamines.
How antidepressants really work
All common antidepressants increase one or more of the three major monoamines (noradrenaline, dopamine, serotonin).⁵ Even though we know their molecular mechanism, there is a widespread misconception about how antidepressants work.
Most people consider antidepressants to be “a pill to feel well”. It is true: Antidepressants do help you “to feel well”. However, not in the way most people think.
If you (lawfully) take MDMA, you will immediately feel wonderful because of its direct effects on our subjective moment-to-moment wellbeing hitting us like a truck. Antidepressants, however, work differently. While there certainly is a direct subtle increase in moment-to-moment wellbeing, their indirect effects on your objective life situation are as -and perhaps even more- important. However, these indirect effects are rarely taken into account.
Let’s use the most commonly prescribed class of antidepressants as an example. Serotonin-reuptake-inhibitors (SSRIs) block the transport protein responsible for the reuptake of serotonin. If this protein is blocked, serotonin accumulates in the synaptic cleft in all the neural networks innervated by serotonergic neurons. Many of these networks are networks responsible for activating the stress and fear-response (e.g. subnetworks of the amygdalae, limbic cortices, etc.).
As levels of serotonin (mostly an inhibitory neurotransmitter) increase, activity in these networks is downregulated, which causes their baseline-activity to be lower. This downregulation then reduces your tendency to ruminate, stress, and worry…because the mind is what the brain does.⁶
Note: All this also applies to hormones. In fact, optimizing hormones is more powerful than any antidepressant we have.
Over time, this reduction in stress and anxiety then catalyzes the evolution of new thinking patterns. You become less worried, calmer. You start to view things differently and ruminate less. Because of all of this, not only your inner life changes but, over time, also your outer life, your objective life situation.
You begin to act differently. You might contact that friend you have not talked to in a long time, building the high-quality relationships all of us need so deeply. You might take back on that hobby you had stopped for years. You now finally have the energy and motivation necessary to go out and productively tackle whatever needs to be tackled (which is almost impossible to do if you are chronically anxious, lethargic, or unmotivated).
So, in a way, taking an antidepressant is like tuning up the motor, but if the car does not go anywhere, it will not matter much.
With this combined effect of a changed inner life (e.g. a change in thinking patterns, how you tend to frame things) and a changed outer life (e.g. a change in relationships, how you spend your time), the depression gradually lifts. Hopelessness and helplessness slowly fade and a new outlook on life starts to develop. Gradually, you tend to like your story and the character they play in it. All catalyzed by a change in neurobiochemistry.
Knowing all of this, we can now summarize how antidepressants really work. Treatment (whether lifestyle, pharmaceutical drugs, hormones) → your neurobiochemistry changes (instantly) → your your moment-to-moment wellbeing changes (hours to days) → your thinking patterns change (days-to weeks) → your behavior changes (months) → your life situation changes (months to years) → the combination of all of these things changes the story you tell yourself: your level of happiness/depression over time.
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Should you take antidepressants?
Let’s say you are a chronic insomniac. You have tried out countless different remedies, lifehacks, and “natural” supplements but other than the transient short-term improvement, nothing really seems to provide lasting relief.
The lack of sleep makes you fatigued during the day, you cannot focus, your willpower is low. Your metacognition is awful and your attention span is non-existent. You are much less efficient and effective at work. The fatigue makes you more withdrawn and irritable and therefore your social life suffers as well.
Furthermore, the increased sympathetic drive and hypercortisolism wreaks havoc on our metabolic health, which along with your suboptimal diet and exercise regime, led to you bordering on metabolic syndrome. You have read how “bad” all this is and that it is supposed to drastically increase your risk for neurodegeneration, cardiovascular disease, and cancer, the three of which are responsible for most deaths in Western civilization.
You thought about taking sleeping pills. However, after doing some research online, you decided against it. They just seem to have many nasty side effects, cause tolerance build-up, interfere with memory consolidation, and people cannot get off them. They are just simply “bad” for you.
True, all of these are legitimate concerns, and relying on sleeping pills is “bad”. But “bad” compared to what? The question should not be, whether something is “good” or “bad”, but what is worse? For your health, your wellbeing, and your life? Sleeping badly for years on end (including all the direct and indirect consequences this entails) or taking sleeping pills?
True, all of these are legitimate concerns, and relying on sleeping pills is “bad”. However, bad compared to what? The question should not be, whether something is “good” or “bad”, but what is worse? For your health, your wellbeing, your life, your impact on others? Sleeping badly for years on end (including all the ripple effects this entails) or taking sleeping pills?
Most of us only look at this side of the equation. What are the risks of not solving your sleep issues? What are the opportunity costs of inaction? In the end, it is a complex calculation of tradeoffs, but there are risks from doing nothing as well. The last point is often dismissed.
Let‘s go back to depression. In major depression, both your inner life and outer life go downhill. Regardless of current years being lost, there is also the risk of massive damage to be done to your future life situation (e.g. development of addiction, social life, career, bad lifestyle habits leading to health issues, etc.), which persists even after the period of being depressed is over.
Furthermore, even though many people have a weird “inner resistance” against treating mental health issues artificially, there is one more thing most of us do not consider. It is not just about you. The way you act, what you do or do not do, what or what not you contribute to others, the resources you consume -they will all have an impact on the life of many others as well, either directly or indirectly. And if taking a pill truly helps you and/or others, so it might be the lesser evil -all things considered.
Note: All this is regardless of the fact that many people do not need to take pharmaceutical drugs for life but often can come off after things have stabilized somewhat.
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Depression: A neurobiochemical disease?
Relationships are what it is all about, I hear you say. Well, if you are chronically lethargic, anxious, or unmotivated, you will not want to interact with others in the first place. Plus, others will not want to interact with you.
The way we tell our story is what it is all about! Well, if your energy and mood are always crap, so will your thinking patterns and outlooks on life follow suit. And therefore the story you tell yourself.
Purpose and meaning are what it is all about! Well, why do you think people in their early twenties (when hormones are at their peak) have zest for life, have purpose, are more prone to dreaming, and ready to conquer the world? Why do you think a midlife crisis happens around the time when certain hormones experience major drops?
Of course, you cannot “bio-hack” yourself out of every negative state. For example, while most of the time I feel great (biologically speaking), when my girlfriend recently left me for someone else, I felt depressed and sad for weeks, despite still feeling “great”. All the antidepressants or hormones in the world could not have changed that. However, my point is this: Firstly, great vitality and neurobiochemistry change how we view things. This alone can make a world of a difference because “there is nothing either good or bad, but thinking makes it so.”. Secondly (and perhaps more importantly), a great vitality and neurobiochemical state change how we respond.
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Becoming different: Changing your autopilot.
We have now seen how the right (or wrong) intervention (e.g. hormone, neuropharmaceutical) can change neurobiochemical equilibria in a certain way to completely change someone’s outer and inner life over time. However, this can also change the person itself.⁶
In his mid-twenties, a good friend of mine was started on the stimulant drug lisdexamfetamine for unrecognized ADHD. Just by altering neurobiochemistry, he is now more focused, less rigid, less judgmental, a little more empathetic, more self-confident, ruminates less, and able to be present without unnecessary worries constantly interrupting.
But the crucial point is this: All these changes are automatic. No need for painstaking unlearning, relearning, and habit formation. No need for anything other than taking the medication.⁷
If we make sustained alterations to our neurobiochemistry, whether “naturally” through lifestyle changes (e.g. sleep, exercise, changes in diet, etc.) or whether through more “artificial” intervention (e.g. hormones, antidepressants, stimulants, daily caffeine or weed), over time we become different. Our autopilot becomes different.
As both the brain begins to rewire and also new thinking patterns start to form, gradually, our personality changes -often without us being aware. It is often not even us who notice the change in our personality but rather other people. They can tell something is different. They can tell that we are different.
This automatic change to our personality and behavior is quite unlike any intentional changes we try to make. No need for any conceptual knowledge from self-help books or other strategies of to-dos and to-not-dos. We can think, talk, and even write about it but in real-life, all this conceptual knowledge does not help us that much. Usually, real, tangible change is meager at best. Even after reading 10 books about how to be more mindful and compassionate, quite likely we are still the same old, mindless asshole when somebody is rude to us, having acted in our habitual autopilot-mode, long before we can pull out our nice and neat little strategies about how to win friends and influence people.
However, if certain aspects of our (neuro)biochemistry change, then our autopilot mode, our baseline, our natural spontaneous intrinsic self changes. We became different even if we are unaware of it.
Let’s say, some vicious scientist secretly injected you with a serotonin reuptake inhibitor while you sleep. He keeps track of the changes happening to you and compares it to your identical placebo-treated clone in an alternate, parallel universe.⁸
As old habits die hard, change is likely slow. But relentless. Cumulative. And given enough time will elapse, slowly brain wiring is altered, and thinking patterns change. These mental changes spin-off many behavioral changes, which ultimately affect your “outer” life (e.g. relationships, hobbies, productivity).
So, even if you stopped treatment (e.g. hormones, antidepressants), due to a combined effect of all these things (i.e. the changes in your brain wiring + changes in your thinking patterns + changes in your habits + changes in your life situation), the effects on your behavior and personality will quite likely persist for some time -certainly months, perhaps years…and maybe even longer if mental and behavioral habits are maintained by additional deliberate effort on your side.
This can be compared to building muscle with the use of steroids: Although steroids by themselves will cause an automatic change in muscle growth (the same way as antidepressants do with brain wiring and thinking patterns), if combined with a proper exercise and nutrition regime (i.e. conscious effort on your side), these gains are synergistic. Even if you then stopped the steroids, just maintaining the muscle would only require low-level effort and is much easier than building it in the first place (which perhaps would not even have been possible to such an extent without the use of an exogenous crutch). Your physique will show signs for a long time -even after stopping.
The downsides of feeling “too” well
In addition to changes in neurobiochemistry affecting your brain, thinking patterns, habits, and life, changing your neurobiochemistry also changes the subjective micro-universe you are living in. It changes your moment-to-moment experience.
From an experiential point of view, the reality of your life is always now. In fact, your life is essentially just a string of individual moments right next to each other. Given this, feeling good from moment to moment has value in itself.⁹
However, while there is nothing wrong with feeling well all the time and while it might sound tempting and even desirable, feeling “too” well does also have its downsides.
After my hormone optimization protocol was more or less complete (How To Fix Your Hormones: The Ultimate Guide), I had times when I just felt “great” (especially considering the stark contrast I was coming from). However, feeling “great” also made me overly confident and left me blind to possible negative consequences of my actions, which often led to me doing things I now regret. For example, during my “high” I made a risky investment in stocks and lost around €10.000, which, without having felt “great”, I likely would not have done.
Feeling “great” also made me more impulsive. More than one time I said something I later wished I had not. For example, one time I said something to my girlfriend that really hurt her. It hurt her so much that it broke her heart. I was not just impulsive but also quite unempathetic and insensitive because, feeling so “well” myself, I could not see how she could possibly be suffering. As the most beautiful soul in the universe was crying into my shoulder, I felt nothing. Red flag.
Fortunately, as my neurobiochemistry stabilized and the “honeymoon” phase was over, my impulsivity, emotionality, and empathy all returned to normal. However, reflecting on this period was a wake-up call. Whereas before maximizing my biological well-being was my main goal, now I know that, while tempting, it is also dangerous. Not just for you but also for your loved ones and perhaps even for society as a whole.
Furthermore, there is one more thing most people do not consider. Periods of suffering can be very productive to your future life. In retrospect, these are often major times of identity formation, growth, and change. They force you to adapt and are often times when many crucial decisions are made from which you might benefit later in life. If you feel “well” all the time, you might be (unintentionally) eliminating these transformative periods.
However, to be fair, let’s also consider the other side. While it is true that for many of us a lot of beneficial growth happens reactively (as a reaction to suffering), proactive growth (growth through positive action from intrinsic motivation) is possible as well. And such growth is certainly more likely if you feel “somewhat well” because you do not worry too much, are motivated, and are more ready to take action.
Therefore, long periods of time where you feel “well” also have their upsides: you can be incredibly productive and whatever you do or create during these periods remains (e.g. open up a company, write a book, study lots of material, earn a lot of money, the Nazis using truckloads of amphetamines being able to do their Blitzkrieg-thing and in the process conquering half of Europe in just a few months).
Another upside of feeling well is that you can simply enjoy life as it is now…¹⁰
So, how “well” is optimal? How “well” does strike the right balance between you doing things that are conducive to your future life while also being able to enjoy your life in the present moment? What degree of “well” maximizes the area under the curve of your happiness function? What degree of “well” maximizes the area under the curve of productivity?
Well, there is no way to tell. The second-or third-order consequences simply cannot be predicted. However, in my opinion, feeling “quite well” has overall netbenefits…despite there being some tradeoffs and dangers.
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Footnotes
- At the time, I was replacing my thyroid hormones with the active thyroid hormone triiodothyronine (T3) instead of thyroxine (T4). T3 is the active thyroid hormone and has a half-life of less than one day, compared to T4, which has a half-life of over a week. Monoamines (noradrenaline, serotonin, dopamine) rise and fall with levels of thyroid hormones. As these change, so does calmness (serotonin), motivation (dopamine), and alertness (noradrenaline).
- Scientific explanations:
–Sickness: → inflammatory mediators → reduction in monoaminergic signaling (noradrenaline, dopamine, serotonin) → the altered neurobiochemical state is reflected in thoughts about life in general
– Sleep deprivation: → the HPA-axis and the sympathetic nervous system are kicked into overdrive → the altered neurobiochemical state is reflected in thoughts about life in general
– Fasting: → food → sensory and endocrine signals sent to the brain → the brain is suddenly flooded with serotonin → the altered neurobiochemical state is reflected in thoughts about life in general
– Intense workout: → increase in endorphins as well as an increase in serotonergic tone → the altered neurobiochemical state is reflected in thoughts about life in general
– Cold shower: →drop in core body temperature → (nor)adrenaline, and dopamine is through the roof → the altered neurobiochemical state is reflected in thoughts about life in general - Certain genetic variants (e.g. SERT, MAO, COMT, D2R) quite strongly correlate not only with subjective levels of happiness, but objective life success as well. From very early on, carriers of these alleles have their lives nudged into a different direction compared to the life of their cloned self in an alternate, parallel universe, who by chance happened to be the carrier of a different version of these genes. This applies to a vast number of receptors for neurotransmitters, the many enzymes involved in neurotransmitter synthesis pathways, the countless relay proteins in the subsequent intracellular signaling cascade, etc. The same also holds for every step of hormonal expression, regulation, signaling, number of cells involved at every step along the way. A life altered. Either for the better or the worse.
- There is a reason why putting people on a tryptophan depletion diet ( → cessation of endogenous synthesis of serotonin) over time leads to the vast majority of them becoming depressed. It is not how they “subjectively” feel but due to the way they think, act, and behave in real-life, their life situation changes over time as well. There is a reason why around 90% of people who are on pharmacological doses of glucocorticoids develop depression over time -similar to what occurs with hypothyroidism or hypogonadism ( → postpartum depression, PMS, “lowT”). Conversely, around 70% or so of depressed people respond quite well to monoaminergic drugs (antidepressants). Again, it is not just the conceptual changes (e.g. differences in how they frame things) but over time their monoaminergic state will be reflected in their “objective” life situation.
- Ketamine seems to be an exception. Psychedelic drugs also are unconventional antidepressants but they work more like “psychotherapy for a year compressed into a single afternoon”.
- Science doesn’t care whether you believe otherwise.
- The same way an SNP for MAO-A or COMT or SERT or D2R would ripple out to affect your brain wiring and thus your personality (as well as every aspect of your outer and inner life), so does any neuropharmaceutical substance that is taken regularly.
- Because his neurobiochemistry changed, he was a slightly different person from early on. For example, the first few days after commencing treatment, one morning, he dropped his jelly sandwich, which fell jelly-side down on the floor. Normally, this instance of “bad luck” would have peppered his whole morning, even though he knew perfectly well that there was no need to be pissed about “bad luck” because falling sandwiches simply behave according to gravitational laws. Usually however, it did not matter what he knew but what he felt took over. Now on treatment, he remained calm and rational (as a “normal” person would) and simply made himself a new sandwich.
- For sure, your personality, as well as your alternate clones‘ future, will be different. Ever larger differences the longer the experiment runs.
- Many people have no problem engineering this moment-to-moment micro-universe to their liking. In fact, this is what recreational drug use is all about.
- Although perhaps at the price of making tradeoffs with our future. For example, hippies often stumble toward failure and regret, despite being genuinely happy during the few years when they “do their thing”.
About the author
My goal with all my writing is to point people in the right direction towards removing biological shackles holding them back from becoming a better version of themselves, living life fully, and being better contributors to humanity.
These articles took thousands of hours to create (let alone the years of self-isolation to gather all this information from hundreds of different sources, distill it, and then synthesize it).
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