Hackernoon logoWhy Depression Is A Chemical Imbalance. But Not The Way You Think. by@thingsvarious

Why Depression Is A Chemical Imbalance. But Not The Way You Think.

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@thingsvariousThingsvarious

Medical student. Biohacker. Addicted to learning about various things. Started writing instead of just consuming.

Update 2020: There is an updated version of this article available. HERE.

At the root of depression is hopelessness (it will never get better) and helplessness (there is nothing I can do about it).Why Depression Is A Chemical Imbalance: Lessons From MDMA, Self-experiments, Bipolar Disorder. Depression is a chemical imbalance. However, not in the way you think.

About the author: I am a final year medical student. 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. You can read more about how hormones destroyed and saved my life here.
Mental health is the strongest individual predictor of life satisfaction…and given that the mind is all we have, mental illness can take away our lives. In this article I will make the case that mental illness is strongly connected to disorders of brain circuits and metabolism and consequently depression (and other mental illnesses) is mostly a “chemical imbalance”. However, the connection is not as straightforward as you might think.

The mind is what the brain does.

Note: 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.

In my very early days of hormone replacement, I was on the fence. I needed time to think. Time to ponder if I wanted to keep doing this for the rest of my life. Time to reflect on why my life was falling apart.

To do this, I had locked myself up in a monastery for some time. After some sleepless nights, I figured I just could not see myself doing this for the rest of my life.

Note: At the time, I was replacing my thyroid hormones with the active thyroid hormones 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.

Invigorated by the stimulating effects of the active thyroid hormone that I had started only a few weeks or so ago, I decided to quit it cold turkey. As it turned out, this was a bad idea.

“Do I want to replace my hormones for life?… Will I even be able to? What if an apocalypse happens and I lose access to all the stuff I need?…What if I have severe side effects down the road? Will I wreck my health?… Am I fake? What will my wife say one day? My kids? Will I even be fertile? Will I even find a wife?… 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 suddenly (and stupidly) quitting the active thyroid hormone cold turkey, my body temperature had dropped to below 35C within just a few days. To maintain core temperature, over the short-term, our bodies use the sympathetic nervous system.

This means my body and brain were quite suddenly overrun with adrenaline.

I was led to believe that the shaking, the rapid heartbeat, the palpitations, the feeling of being choked were simply conjured up by my thoughts. But this was not the case. It was actually the other way around.

Note: Monoamines (noradrenaline, serotonin, dopamine) rise and fall with levels of thyroid hormones. As these change, so does mood/calmness (serotonin), motivation/drive (dopamine), and alertness/energy (noradrenaline).

In fact, all these destructive self-doubts and dark outlooks on life were a reflection of my biochemistry. A consequence and not a cause. With such a level of adrenaline cruising around my bloodstream for “seemingly” no reason, one can not not get anxious.

Let´s go back to a few weeks before this event. 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” (bordering on hypomania), now, however, it was the opposite (anxiety and depression, even thoughts about suicide for a brief moment.).

Let´s go back even further. A few months before all this, my life was dull and grey.

From just trying to get by (a few months before) to thoughts of grandeur (weeks before) to extreme self-doubt (now). Funny, because the factual/objective content of my life had not changed much 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 three periods, neurobiochemical changes were reflected in my thoughts and outlooks on life, swinging from barren wastelands, to heaven, to hell.

I slowly reintroduced the active thyroid hormone.

As my neurobiochemistry reversed again, so did my thoughts, outlook, and thinking patterns. For a brief time, I felt perhaps a little “too well” again. I was incredibly grateful to be alive and could not understand anymore, what the heck I had so been anxious about.

Even though now I knew exactly what was happening neurobiologically, I was carried away by my emotions. The subjective experience was too intense, visceral, and raw for me to be able 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 unfortunate experience, I learned three lessons.

First, hormones (or drugs that mess with your neurobiochemistry) are nothing to be messed around with, especially if you don’t 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 your life and the life of others.

Second, 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 and often in rapid succession (and minor versions of this cycling are experienced by the fertile half of the planet, every single month).

Third, we are deeply biological creatures. Our emotions, thoughts, outlook and thinking patterns are at the mercy of our neurobiochemistry and its changes (For more, read how hormones destroyed and saved my life).

While the sudden withdrawal of active thyroid hormones is certainly not generalizable to many others, 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 was my baseline?

Most likely, I would have developed a severe anxiety disorder quite early in my life. I would have always tried to battle my neurobiology, eventually realizing I was powerless and stood no chance against these forces and likely being put on psychiatric drugs (if I was lucky).

On the other hand, how would my life have turned out if my baseline brain state had been as it was during those weeks of optimism?

Many lives are wrecked from very early on by genetic or developmental aberrances in neurobiochemistry.¹ Being a medical student, I knew this before. But I “knew” it in a way medical students “know”. During my adventure with T3, now I could feel it. That is far beyond any textbook knowledge.

I viscerally experienced what this actually means for someone’s subjective micro-universe — the anxiety, the self-doubt, and the choking. Not just cold statistical correlations detached from any tangible reality.

While most of you likely cannot relate to what it feels like going from euthyroidism to severe hypothyroidism in just a few days, here is something the more audacious of you might be able to relate with: MDMA.

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.

Note: If you have never taken MDMA before, think about a time when you tried to beat your addiction to weed or caffeine. Battered by the side effects, perhaps after only a few days you give in. Let your first puff (or your first sip of coffee) be the PG-13 version of MDMA.

Let the days before this legal experience represent your baseline regarding 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 and 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. In fact, many of your problems disappear. It is not that you do not remember them. No, you are in fact quite lucid and very aware of your problems. However, now you are full of energy, motivation, euphoria and as your neurobiochemistry has changed, you view these problems through a completely different lens. The “what” did not change, but the “how you see it” did.²

Let´s fast forward 24h or so to a time when many of your monoamine stores have been depleted. Your neurobiochemistry has changed again, but now in the opposite direction.

You now feel 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. Your tendency to be optimistic or pessimistic about your life and future. In both instances, your views, thoughts, and outlooks on life are secondary and simply a puppet of your neurobiochemistry.

Note: PG-13 version: Has euphoria ever crept up on you after your first sip of coffee? If you have ever tried to wean yourself off caffeine, you will know that the opposite is true as well. And once you reintroduce caffeine and take that first teeny-tiny sip of coffee, the grey world turns into color again. You are excited about life, even though just minutes ago you were semi-depressed and your outlook was 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 as the MDMA, read on.

To get non-lame stuff about becoming the best version of yourself, sign up here.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 a long time without eating?

Have you ever gone for a long, intense workout and the following boost in mood often 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 3.

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. Every conscious state emerges from a 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?

From these examples it is easy to predict that 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 things then have powerful ramifications on every domain in our life and also on why our life turned out the way it did.

Note: For more about this, read The most important lesson I have learned from replacing my hormones.

To better understand the chronic effects of these “chemical imbalances” I think the following disorder illustrates my point quite perfectly.

Bipolar Disorder

If you do not personally know anyone with bipolar disorder, then you might know one of the following people who suffered from it: Winston Churchill, Jimi Hendrix, Curt Cobain, Marilyn Monroe, Ernest Hemingway, Vincent Van Gough, or Kanye West.

Briefly, 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 (high monoamines), they feel more than “well”. They are motivated. They are creative. They do. They come up with countless projects. They start companies. They do things that are irrational and stupid to the outside observer.

As their monoamines oscillate downward again, so does their energy and motivation. At this point, they are depressed and listless, a pale reflection of what they were in their high state only a few months 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 are 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 strongly and dynamically fluctuating. Most of us, however, have a baseline state that is more or less constant and stable. Therefore, our energy, mood, and motivation, in general, do not cycle much (unless you are an ovulating female).

This state of baseline neurobiochemistry determines (or at least strongly influences) how we feel on a daily basis (e.g. depressed, listless, motivated, enthusiastic), which strongly influences our actions, which then, in turn, determine how our outer and inner life turn out.

Note: Slight changes in our baseline 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/sleep/exercise, whenever we ingest any substance that influences our neurobiochemistry, etc.

My point is this: positive vs. negative thoughts/moods/outlook are (more) often caused by our underlying neurochemistry rather than them being the direct cause for us to feel good or bad. 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.

This means that if we are (biologically) in a bad mood (first and foremost related to low monoamine levels), our thoughts and outlooks will follow suit.

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. At the very least, they will put you in a state of mind from which you can more calmly and objectively look at whatever problems you have.

Biology, your life, and happiness

Science claims happiness to be determined to 60–80% 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). While prone to confounders, this is the best that science can do. What these studies tell us is this: If if we were able to derive an equation that predicts people’s happiness best, genetic factors ( → biological factors) account for over one half of it.

This means that, on average, biological factors are by far the most heavy-weighted factor determining someone’s happiness level. In fact, while there are certainly many exceptions, for the average human being, biological factors are more important than all the other factors combined.⁴

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.

Genes’ effect on happiness is not by making you “happy” in the same way recreational drugs make you “happy”. The effects genes have on our level of happiness are to a large extent indirect. Genes influence our biochemistry. Our biochemistry though does not just influence our moment-to-moment wellbeing (e.g. energy and mood) but also our thinking patterns and therefore the way we act. Therefore, over time, they influence our overall life situation (wealth, relationships, status, profession, etc.).

The ripple effects of biology

Genetic/biological factors ripple through our lives the same way an earthquake ripples through the Earth’s crust. However, they can also affect our life the same way the flaps of a butterfly in Mexico can cause a hurricane in Texas (for more, read the introduction of The Most Important Lesson Learned From Replacing All Of My Hormones).

No domain of our lives is out of biology´s purview. From energy levels, mood, health, IQ, looks, brain wiring, cognition, motivation, concentration, personality traits, etc. Among other things, all these strongly influence the thinking patterns we have evolved over the years and also the lifestyle choices we make, our decision-making, our likeability, our emotional reactions, our drive, how outgoing we are, etc. Together, over time, this influences every aspect of our life, every single day.

People high up in social and economic ranks are people with impressive “conventional” life success (wealth, status, relationships). These people 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 most of them are 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 unwillingly (or willingly) settle for the mediocre (or less) quite early in life.

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. Why? Because these early founders, on average, had greater levels of energy and motivation compared to the people they left behind in their home country. The energy and motivation necessary to set for a brave new world. 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 that.

Hormones

Due to my personal experience, I argue that from all the biological factors, hormone levels are the most powerful. This connection between hormones and happiness is so incredibly important that it deserves to be mentioned. (I devoted a short section in it here: How To Fix Your Hormones: The Ultimate Guide.)

Links to practical guides (article continues below)

How To Fix Your Hormones: The Ultimate Guide (main article)
Brief Overview Of Different Hormone Therapies
How To Replace Thyroid Hormones
How To Replace Cortisol&Adrenals
How To Replace Male Sex Hormones
How To Replace Female Sex Hormones
How To Replace Growth Hormone
Different Types Of Fatigue For Different Hormone Deficiencies
A Diet That Works For Everyone

How antidepressants really workSome background:

In the same way that happiness is not just “genetics”, depression is not just a chemical imbalance. Depression is a catch-all term for countless different syndromes, all quite distinct from each other. The only common denominator between depressed people is “prolonged subjective suffering”.

For my personal understanding of psychiatric disorders read my short excerpt about it here.

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 depression, 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.

Note: Briefly, dopamine makes us feel “I am motivated”, serotonin “I am calm and relaxed.” and 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 is the way it is, perhaps starting as early as the second month of pregnancy. Unless we are using a neuropharmaceutical drug on a daily basis, the main factor that determines our individual baseline level of any of these monoamines at any given point is our hormones (as well as the balance between them). As our hormones change so do our monoamines.

As I was changing my hormones around, my monoamines were all over the place. Consequently, my energy, mood, motivation, etc. were all swinging quite a bit.

Let´s look at the examples from above. As I withdrew the active thyroid hormone, dopamine and serotonin took a nosedive, whereas noradrenaline soared. With MDMA usage, dopamine and noradrenaline accumulate in the synaptic cleft, while serotonin is additionally released. 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 these changes quite instantly.

How antidepressants really work

All common antidepressants increase one or more of these three 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”. Antidepressants do help you “to feel well” but not in the way most people think.

If we take MDMA, we will immediately feel wonderful because of its direct effects on our subjective moment-to-moment wellbeing. Antidepressants, however, work differently. While there certainly is a slight increase in moment-to-moment wellbeing, their indirect effects on our objective life situation are as important, perhaps even more important. However, these indirect effects are rarely taken into account.

Let´s use the most commonly prescribed 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 triggering the stress/fear/flight/fight-response (e.g. subnetworks of the amygdalae, limbic cortices, etc.). As levels of serotonin, which is mostly an inhibitory neurotransmitter, increase due to the action of the SSRI, the activity in these “stress”-networks is downregulated, which causes their baseline-activity to be lower, which then reduces our tendency to ruminate, stress, and worry…because the mind is what the brain does.⁶

Over time, this reduction in stress/anxiety then catalyzes the evolution of new thinking patterns. People are less stressed, calmer. They start to view things differently. They ruminate less. Because of all of this, people act differently. They might contact that friend they have not talked to in a long time, building high-quality relationships all of us need so deeply. They might take back on that hobby they had stopped for years. They 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 -all of which are predominantly biological issues).

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.

Because of all of this, not just their inner life changes but over time also their outer life, one´s objective life situation. With this combined effect of a changed inner life (for example a change in thinking patterns and how one tends to frame things) and a changed outer life (for example a change in relationships or how one spends one´s time), the depression gradually lifts. Hopelessness and helplessness slowly fade and a new outlook on life starts to develop. Gradually, people tend to like their 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, drugs, hormones) → neurobiochemistry changes (hours to days) → moment-to-moment wellbeing changes (days-to weeks) → thinking patterns change (months) → behavioral changes (months) → life situation changes (months to years) → the story you tell yourself changes (months to years) → the combination of all of these things changes your level of happiness/depression over time (months to years).

Note: Everything I wrote about antidepressants, also holds for hormones. In fact, replacing/restoring hormones to youthful levels is more powerful than any antidepressant we have. For how to fix your hormones, read here.

Should you take antidepressants?

Let´s make an analogy. Let´s say you are a chronic insomniac. You have tried countless different methods, hacks, supplements but other than a transient short-term improvement, nothing really seemed to work.

The lack of sleep makes you fatigued during the day, you can’t 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.

In addition, the negative effects from the increased sympathetic drive and chronic hypercortisolemia wreak havoc on your metabolic health, which, along with your suboptimal diet and exercise regime due to a lack of willpower, cause you to border on metabolic syndrome. You know how “bad” all this is and that it is supposed to drastically increase your risk of neurodegeneration, cardiovascular disease, and cancer, the three of which kill around 80% of people in Western civilizations.

You have thought about taking sleeping pills, but after doing some research online, you have decided against them. They just seem to have too many side effects, cause tolerance, interfere with memory consolidation, and often, people cannot get off them. They are just “very 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?

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.

Note: All this is regardless of the fact that many people do not need to take drugs for life but often can come off after things have stabilized somewhat.

Depression: A neurobiochemical disease?

Relationships are what it is all about, I hear you say. Well, if you are chronically lethargic or 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 about ourselves 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.

Purpose and meaning are what it is all about! Well, why do you think people in their early twenties (when their 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 “biohack” 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.

Becoming different: Changing our autopilot.

We have now seen how the right (or wrong) intervention (e.g. hormone, neuropharmaceutical) can change neurobiochemical equilibria in a certain way to, over time, completely change someone´s outer and inner life. However, this can also change the person itself.⁷

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, 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. In fact, no need for anything other than taking the medication.

Because his neurobiochemistry changed, he became 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.

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” deliberate intervention (e.g. hormones, antidepressants, stimulants), over time we become different. Our autopilot becomes different.

Gradually, our personality changes, often without us being aware. In fact, it is often not even us who notice the change in our behavior and 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. In fact, 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 (or what have you) 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 slow but relentless. Cumulative. 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 brain wiring + changes in thinking patterns + changes in habits + changes in life), the effects on your behavior and personality will quite likely last 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: even if you stopped the steroids, just maintaining the muscle would only require low-level effort and is much easier than building it in the first place. 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. Your physique will show signs for a long time.

The downsides of feeling “too” well

In addition to changes in neurobiochemistry affecting our brain, thinking patterns, habits, and life, changing our neurobiochemistry also changes the subjective micro-universe each one of us is living in. It changes our moment-to-moment experience. It changes. From an experiential point of view, the reality of our life is always now. In fact, our 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

While there is nothing wrong with feeling well all the time and while it might sound tempting and even desirable, there are downsides to feeling “too” well too.

After my hormone replacement 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 stuff 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. In fact, 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 or others 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 “engineering” myself to feel very well all the time is tempting, it is also dangerous. Not just for you but also for your loved ones and society as a whole.

And there is one more thing most people do not consider. Periods of suffering can be very “productive” to one´s future life. In fact, in retrospect, many people say that their worst times were the times they grew in character the most. These times give us identity and meaning. Furthermore, these times force us to adapt and thus are often the times when many crucial decisions are made from which we benefit later in life. However, if we feel “well” all the time we might be (unintentionally) eliminating these transformative periods.

However, let´s also consider the other side. While it is true that for many of us lots of growth happens reactively (as a reaction to suffering), proactive growth (growth through positive action from intrinsic motivation) is certainly possible as well…and such growth is certainly more likely if you feel “somewhat” well because we do not worry too much, are motivated and are more ready to take action.

Furthermore, long periods of time where we feel “great” also have their upsides: we can be incredibly productive and whatever we 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).

A third upside of feeling well is that we can simply enjoy life as it is now…Although perhaps at the price of making tradeoffs with our future.¹⁰

So, how “well” is optimal? How “well” strikes the right balance between us doing things that are conducive to our future life while also being able to enjoy our life at the moment? What degree of “well” maximizes the area under the curve of our 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 just cannot be predicted. However, in my opinion, feeling “quite” well has overall net benefits…despite there being some tradeoffs and dangers.

For feedback, inquiries, and questions: hormetheus@gmail.com

Footnotes.The earlier in life these changes occur, the more powerful the effects.You even see putative “solutions” to your problems and you are eager to tackle these in the future.Scientific explanations: 
- Sickness → inflammatory mediators → reduction in monoaminergic signaling (noradrenaline, dopamine, serotonin) → altered neurobiochemical state is reflected in thoughts about life in general.
- Sleep deprivation → the HPA and the sympathetic nervous system are kicked into overdrive → altered neurobiochemical state is reflected in thoughts about life in general.
- Fasting → food → sensory and endocrine signals sent to your brain → your brain is suddenly flooded with serotonin → altered neurobiochemical state is reflected in thoughts about life in general.
- Intense workout → increase in endorphins as well as an increase in serotonergic tone for a few hours → altered neurobiochemical state is reflected in thoughts about life in general.
- Cold shower →noradrenaline, adrenaline, and dopamine through the roof → 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 homozygote for the major allele. This applies to a huge number of receptors for neurotransmitters, the many enzymes involved in their synthesis pathways, the countless relay proteins in the subsequent intracellular signaling cascade. The same also holds for every step of hormonal expression, regulation, signaling, number of cells involved at every step along the way. Rarely do these people know. A life altered. Either for the better or the worse.Ketamine -and some others- 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.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.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.

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