
Is serotonin the happy brain chemical? - jimsojim
http://theneurosphere.com/2015/11/14/is-serotonin-the-happy-brain-chemical-and-do-depressed-people-just-have-too-little-of-it/
======
bluedevil2k
SSRI's in my opinion are not the future of antidepressants. They work by
indiscriminately increasing serotonin levels in the synapse, thereby
activating every single serotonin receptor (5-HT). While you get the anti-
depressant effect by increasing the activation at the 5-HT1 receptor, you also
get the negative side effects of SSRI's since it activates 5-HT2c receptor
(weight gain), 5-HT3 receptor (nausea), and sleep issues.

The future of the antidepressants lies in chemicals that increase serotonin at
the 5-HT1 receptor (lowering depression) without affecting the other
receptors. Drugs like mirtazipine and nefazodone attempt to do this by
blocking certain 5-HT receptors (mainly the 5-HT2a receptor, which lowers
anxiety), and as a result make serotonin levels higher and more available at
the 5-HT1 receptor. That's the reason these 2 drugs in particular don't have
the nasty side-effects of SSRI's.

The future of anti-depressants likely lies in the ability to find a drug that
increases activation at the 5-HT1 receptors in certain parts of the brain,
while leaving the rest of the brain and receptors untouched.

~~~
rudolf0
Also keep in mind that depression isn't always caused by serotonin issues or
remediated by increasing serotonin (which is somewhat redundant with this
article, though I think the article paints serotonin too negatively).

For example, if someone has bipolar disorder (or similar issues), they may
have fairly standard serotonin concentration and receptor activation, but an
SSRI may not help much with their depression.

~~~
bluedevil2k
True, but the thought is that the feelings of worthlessness, hopelessness,
even suicide are seratonin related. There are other types of depression like
"don't enjoy things I used to like, lack mental acuity" that may be dopamine
related. And "mopey, lack energy" which may be noradrenaline related.

~~~
rudolf0
>True, but the thought is that the feelings of worthlessness, hopelessness,
even suicide are seratonin related.

Not necessarily true. People on SSRIs can still want to commit suicide after
serotonin rebounds and is at a stable level.

I think complex feelings like despair and self-hatred can't be explained by
just a single neurotransmitter. Serotonin likely plays a role here, but it's
not the only component.

------
joesmo
This is the first honest article I've read on the subject of serotonin and
neurotransmitters in years. It basically concludes what very few people seem
to be aware of: that we do not know what causes depression or anxiety nor do
we know how SSRIs, SSNRIs, or other similar chemicals work. There are, at
best, hypothesis, generally untestable. The idea of chemical "imbalances" in
the brain is, as it has been since its inception, complete and utter bullshit.
The reality is current medical science simply doesn't know, the marketers make
the rest up, and for some reason, most doctors play along. That's how you get
to the popular and completely wrong idea that serotonin is the "happy" brain
chemical. (Of course, if you're aware of the lack of capability in most people
to process complex ideas, you could easily guess that such a simplistic idea
has to be wrong simply from the number of people who talk about it like it's
real.)

~~~
lostinny
Indeed! We still don't understand the causes of anxiety and depression, and
yet far too many doctors simply went along with the "chemical imbalance"
narrative.

SSRIs and related medications can be wonderful tools, but that proves nothing
re: causality and the best long term treatment. Sadly, this battle was lost a
long time ago[1], but it's heartening that people are starting to revisit some
of these debates.

[1] Here's an article from 1999 arguing essentially the same thing re: how
little we understand about mental illness, and how prescribing doctors should
be cautious about oversimplifying something so complex:
[http://www.psychiatrictimes.com/psychotherapy/psychotherapy-...](http://www.psychiatrictimes.com/psychotherapy/psychotherapy-
perspectives-medication-management)

~~~
tcj_phx
Your link seems to make a case for SSRIs causing learned helplessness. It's
been 17 years since this article was written, and the profession is still
working on fixing itself. "Hmm."

Thanks for the link!

------
johnw11
I would like to point out that there is a whole range of non-SSRI medicines
that have significant clinical effects on depression. In particular:

Medicines that promote drowsiness (such as sleeping aids and even the
antipsychotic quetiapine), as sleep deprivation and depression are highly
correlated.

The atypical antidepressant wellbutrin/bupropion, which impacts a whole bunch
of chemicals in the body but notably does not affect seratonin levels. My
personal experience from having taken it is that it makes me more energetic,
similar to a weak amphetamine.

MAOIs, which again impact a whole bunch of chemicals, including seratonin but
notably also melatonin, which is well-known to promote sleep. These are well-
known to be highly effective antidepressants, but are rarely used because they
require the patient to alter aspects of his lifestyle.

The situation is complicated by the fact that the category of depression
consists of a bunch of different symptoms that may be comorbid in many people,
but are not necessarily.

~~~
johnw11
Also, while I don't personally have experience with a lot of illegal drugs, if
you ask anyone who does he will tell you that there are drugs that nearly
instantly make you happy without having to wait weeks for the drugs to have a
subtle effect on your thought processes.

These illegal drugs may or may not be too dangerous to use regularly to treat
depression, but it's worth noting the fact that it's clearly not "impossible"
to make a true "happy pill"

~~~
empath75
Yeah I've been wondering about that. How the hell does mdma work if it's not
serotonin. I always understood that the euphoria was caused by a flood of
serotonin in your brain.

~~~
mrmcd
I can't speak for MDMA, but I have experimented (ok, recreated) with psilocin
(shrooms), 4-ACO-DMT, and DMT, which are all serotonin agonists.

The best I can describe it is that a high enough dose feels like putting your
brain into debugging mode and then cycling through hundreds of circuits
simultaneously. It's not so much "I am experiencing happy now" as "I am
experiencing happy, sad, confused, interested, pulsating colors, fractals,
childlike wonder, fear, and every other cognitive state simultaneously or in
rapid succession."

Some people get very spiritual about it, but I think you kind of have to be a
spiritually inclined person anyway to have that specific experience. I always
saw it more of giving the hardware a good jolt and seeing what falls out. It's
pretty common to go from laughing uncontrollably, to inconsolable sadness, and
back again, fairly quickly. This is where a lot of the fear about "bad trips"
comes from, but I've found you can manage that with practice and having
experienced people tripping with you or babysitting.

I do think there are therapeutic benefits though. Even if there are difficult
periods, I find I always felt happier, more ok with the world and open to new
experiences and attitudes for up to weeks after words. The article briefly
mentions how there's a hypothesis that depression is possibly an effect of
individuals who "over learn" negative experiences and become fixated on
negative outcomes, and this makes a lot of sense to me. Aside from a sort of
"purging" feeling just from such intense bursts of emotions, I could see how
it helped to kind of kick me out of the traps of negative and habitual
thinking and emotions. Maybe it helped my neurons "relearn" there are other
experiences, emotions, and modes of thinking that I can access too?

This is all anecdotal evidence though, gathered while under severe impairment,
so take it with that caveat. I would bet that aside from the legal issues, the
hardest part of investigating things like psychedelics in a scientific way is
that every experience is inherently subjective and personal. Trying to
describe and talk about them gets very squishy very quickly.

------
cel1ne
Serotonine is very old. There are two different genes TPH1 and TPH2 which
encode the enzyme information for serotonine-production, which happens at two
sites in the body. This split is apparently very old and evolved before
vertebrates did.

Serotonine controls a multitude of things including wake-night-cycle, blood
pressure and temperature. It doesn't even only work as a neurotransmitter, but
mechanically as well.

Further reading:
[http://www.ncbi.nlm.nih.gov/pubmed/8768313](http://www.ncbi.nlm.nih.gov/pubmed/8768313)

------
Raphmedia
After feeling very down, so much that I didn't felt like myself, I started to
experiment with herbal supplements. Valerian to sleep, but my problem wasn't
lack of sleep. St John's Wort for mood, but I didn't feel moody.

I tried 5-htp, which from my understanding is a precursor to the biosynthesis
of Serotonin. The effect was immediate. I felt light headed, buzzed even. I
felt as if I had suddenly woken up in a bright new world. I went groceries
shopping could barely keep myself from gaping at all the colours, products and
people. The next day, those effects were gone but I felt fine. Simply fine. I
tried to take more 5-htp, but those strong effects are gone. I am no brain
scientist, but to me this is anecdotal evidence that I was very much lacking
in Serotonin and that this herbal supplement boosted me right back up.

It's not magical, I still feel anxious about deadlines and stressed about hard
to deal with clients. However, some kind of dark blurry veil has been lifted
from my perception of life.

Edit: Since then, I increased my weekly physical activities and improved my
overall eating habits. I can't say if it's directly linked with my increase
(or rather closer to normal) Serotonin but my instinct says yes.

~~~
carleverett
Relevant part of this comment: "I am no brain scientist."

You probably could have had the same effect from a sugar pill.

~~~
Raphmedia
Why would you claim this? From what I have read 5-Hydroxytryptophan seem like
a widely accepted supplement for issues with Serotonin and/or depression and
mood. The only articles that I have found that say it might not be of use are
studies that simply say that 5-HTP is better than placebo but that we can't
say more yet because of lack of researches. Edit: and possible heart valves
issues if you do not take it correctly

"5-Hydroxytryptophan (5-HTP), also known as oxitriptan (INN), is a naturally
occurring amino acid and chemical precursor as well as a metabolic
intermediate in the biosynthesis of the neurotransmitters serotonin and
melatonin from tryptophan."
([https://en.wikipedia.org/wiki/5-Hydroxytryptophan](https://en.wikipedia.org/wiki/5-Hydroxytryptophan))

"Preliminary studies indicate that 5-HTP may work as well as certain
antidepressant drugs to treat people with mild-to-moderate depression. Like
the class of antidepressants known as selective serotonin reuptake inhibitors
(SSRIs), which includes fluoxetine (Prozac) and sertraline (Zoloft), 5-HTP
increases the levels of serotonin in the brain. One study compared the effects
of 5-HTP to fluvoxamine (Luvox) in 63 people and found that those who were
given 5-HTP did just as well as those who received Luvox. They also had fewer
side effects than the Luvox group. However, these studies were too small to
say for sure if 5-HTP works. More research is needed."
([https://umm.edu/health/medical/altmed/supplement/5hydroxytry...](https://umm.edu/health/medical/altmed/supplement/5hydroxytryptophan-5htp))

etc, etc, burden of proof to you...

[https://scholar.google.ca/scholar?q=5-Hydroxytryptophan&hl=e...](https://scholar.google.ca/scholar?q=5-Hydroxytryptophan&hl=en&as_sdt=0,5)

~~~
carleverett
Admittedly my doubts are solely based on the fact that I see the 5-HTP next to
the fish oil pills and other non-FDA approved supplements at the pharmacy. It
fits into the profiled of what I consider "alternative medicine," and
generally I agree with the idea that if alternative medicine actually worked,
it would be called medicine.

You've done more research than me though. I'll defer to your judgment here.

~~~
rudolf0
5-HTP and omega 3 fatty acids (fish oil pills) are not "alternative medicine"
supplements. They're regular medicine supplements. It's believed most people
are probably deficient in omega 3, unless they eat a lot of fish.

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362/)

[http://www.ncbi.nlm.nih.gov/pubmed/17392137](http://www.ncbi.nlm.nih.gov/pubmed/17392137)

In my opinion, the "alternative medicine" label shouldn't be thrown around
recklessly at substances that clearly have psychoactive properties and strong
theoretical or proven mechanisms of action. They may be insufficiently
researched regarding their potential treatment of specific conditions, but you
shouldn't throw them in the same boat as homeopathy or acupuncture or reiki.

I think 5-HTP probably isn't a suitable supplement to treat depression in the
long term (risk of downregulation and cardiac issues), but it's definitely one
form of treatment for many people.

------
gghh
The article presents a possible explaination for why SSRI antidepressants
(which increase the amount of serotonine in one's synapsis) are effective:
serotonine plays a role in how we learn, and

> [people with an] atypical function of the serotonin system may be at risk of
> developing depression or anxiety because they are too good at learning about
> negative outcomes

> Serotonin changes produced by the drug, combined with appropriate therapy,
> might work by allowing patients to learn that the world is not such a bad
> place rather than simply making them happy.

The article continues noting that this would explain a few things, like

> (1) why treatment with SSRI anti-depressants doesn’t tend to increase
> happiness until weeks after depressed patients have begun taking medication.
> Serotonin changes produced by the drug, combined with appropriate therapy,
> might work by allowing patients to learn that the world is not such a bad
> place rather than simply making them happy.

> (2) why some depressed patients generally do not improve when undergoing
> SSRI treatment. Consuming pills in the absence of improvement in life
> conditions or appropriate therapy might in fact make it easier for already
> depressed individuals to ‘learn’ more about the negative events surrounding
> them

> (3) [why we] have no evidence that [simply] increasing brain serotonin
> levels actually improves people’s mood.

The evidence shown to supports this role of serotonin in the learning process
consists of two studies (cited in the article). The first showing that rats
grown in the dark developed abnormal sensitivity to non-visual stimuli, and
that serotinine played a role in the process. The second found that
individuals with a particular genotype affecting the serotonin system were
more likely than others to develop depression or anxiety _only_ if they had
experienced stressful life events.

Betteridge's law of headlines checks out: Is serotonin the happy brain
chemical? No, it (probably) plays a complex role in how we learn about bad
outcomes.

~~~
digi_owl
Sorry but i have to get this off my chest.

This fits me so well. I wonder how many nights i have simply wished i could
think less. That is, stop twisting old events hoping to grab some new
insights, or ruminate about whats to come given X Y and Z.

~~~
dustingetz
Maybe you might view that as strength, something about your brain chemistry
that lets you achieve deeper insight than your peers, and makes you a better
innovator? I say this as someone like you, who replays events in the past or
future, over and over to gain deep insights (or maybe confirmation biases),
and i also wonder if it is related to my seratonin-dopamine imbalances (i have
adhd), as it is very clear that my obsession with understanding the _why_
behind the world is not normal and i wish i could just let it be

------
PaulHoule
I'm not sure that SSRI's make me happy, but I have never believed the
"chemical imbalance" story about them.

I have always been kindof anxious, maybe with a touch of GAD or even social
anxiety, and I when I knew the rug was about to get pulled out from under me,
I started taking an SSRI to increase my resilience.

Under the SSRI I am definitely much less anxious, perhaps even to a fault --
the big benefit I see it that I don't get upset about little things, like I
don't get upset about being stuck in traffic.

------
pif
By the way, triptans (drugs that increase serotonin level) can be very
effective in fighting against migraines. Switching from a splitting head-ache
to nothing in 20 minutes, when instead classic analgesics would do nothing, is
a step towards happiness.

Edit: SSRI -> triptans

------
Nihilartikel
There's actually an old, effective-in-studies, and fairly obscure anti-
depressant called tianeptine that works by enhancing serotonin reuptake, which
lowers the levels. Effectively an Anti SSRI. I hear about it from the
nootropics camp from time to time.

~~~
rudolf0
Unfortunately, tianeptine is not quite the wonder drug people hoped it would
be.

It does increase serotonin reuptake (thus resulting in lower serotonin
concentrations), but this is believed to be unrelated to its anti-depressant
and relaxant effects. You can see a debunking here:
[https://en.wikipedia.org/wiki/Reuptake_enhancer](https://en.wikipedia.org/wiki/Reuptake_enhancer)

Tianeptine was found to simply be an opioid receptor agonist. In other words,
it's just a mild opioid, sort of like codeine. Obviously, opioids and opiates
can improve mood.

But it's a weak agonist, and the opioid receptors it targets are less
implicated in the addiction and powerful euphoria associated with morphine or
heroin. So, taken in low doses (the standard dose is very low), dependence and
tolerance can remain low, and it can effectively improve mood over a long
period of time. But increasing the dose will result in typical opioid
euphoria, tolerance, and withdrawal effects.

Perhaps more importantly, it doesn't treat the root cause of depression in
many people; it merely masks it. Sure, SSRIs often don't treat the root cause
either, though for people with specific serotonin issues, they can. But an
opioid or opiate is always just going to be a "layer" over your depression.

It also tends not to help people who struggle with avolition and lack of
motivation or energy; it may even do the opposite, as opioids are wont to do.

But it will help with your mood. And it not treating the root cause is not
necessarily a bad thing if it improves your enjoyment of life and your ability
to function.

For many people, an SSRI will be more effective than tianeptine. For those who
do not have any serotonin imbalance, tianeptine could be better.

------
CPLX
My main takeaway from this article was that someone also wrote an article
entitled "Chemicals that activate happiness, and how to gamify them" and
somehow thought this was ok.

------
rincewind
Is the zero bit the computer happy bit?

~~~
amelius
I don't know, but I found this to be the interesting bit:

> Depressed and anxious people might simply be too good at learning about bad
> outcomes

> Over the past few decades, researchers have been discussing that mental
> health issues such as depression and anxiety might fundamentally be
> disorders of learning, rather than outcomes of a ‘chemical imbalance’ that
> requires correction by a serotonin boost. Specifically, certain individuals
> which have atypical function of the serotonin system (which might be caused
> by genetic factors or stressful lives) may be at risk of developing
> depression or anxiety because they are too good at learning about negative
> outcomes, and thus are more likely to feel that the world is a bad place if
> they experience negative life events. One of the most talked-about studies
> in the psychiatric literature supports this possibility (6). It found that
> individuals with a particular genotype affecting the serotonin system were
> more likely than others to develop depression or anxiety only if they had
> experienced stressful life events, such as child abuse, unemployment, or
> loss of a loved one. Clearly, having an atypical serotonin system alone
> wasn’t enough – it had to be combined with negative experiences.

~~~
agumonkey
Add paranoid, which mindset is mostly interpreting everything as a source of
bad (worst) outcome.

It also drives thinking into designing "pure solutions" in which the bad just
cannot happen. I applied it unconsciously in software design (recently learned
it was a design philosophy too).

------
NickM
I've noticed a strong pop-psych trend these days of referring to one's own
feelings or experiences in terms of neurotransmitters. e.g. "I'm hooked on the
dopamine rush of such-and-such activity," "I'm feeling blue today, my
serotonin must be low," etc.

This drives me crazy. It's pure pseudoscience, and I hear it from people who
should know better. Scientifically, we have very little idea what chemicals
are actually behind different subjective feelings/moods/whatever. Everyone
would love to believe that the brain operates in a simple, intuitive fashion,
with one chemical for joy, one chemical for sadness, one chemical for anger,
etc., but the reality is _way_ more complex and nuanced.

For example, even something well-studied like dopamine, which has been
strongly linked with the brain's addiction circuitry, doesn't necessarily
stimulate any sort of direct pleasurable feeling as people often infer. It
seems to work in a much subtler way, modulating learning, attention, and goal-
seeking behavior. A recent study found that it doesn't even necessarily spike
when good things happen, but tends to increase in response to unexpected
events, good or bad.

~~~
heimatau
> "I'm feeling blue today, my serotonin must be low," etc. This drives me
> crazy. It's pure pseudoscience,

Yeah. I think it's a pseudoscience too. Even though 5HTP and St. John's Wort
produce a 'happy feeling' to me and many others. It doesn't last. Even with
modern day SSRIs and other depression meds, pill holidays are recommended.
Pill holidays shows me that they are an imperfect solution. I would tell a
person in a wheelchair to 'try and walk it off' for a few days/weeks. That's
unfair to their illness, yet psych does that with their meds.

> but the reality is way more complex and nuanced.

I couldn't have said it better myself. Hopefully, we'll have a medical
breakthrough in psych in the next 20 years. With all the investment, I'm
optimistic.

~~~
tachyonbeam
The reason it doesn't last is that you're building a tolerance. Your brain
tries to adapt so that it can bring you back to "baseline". If such mechanisms
weren't in place, then a change in diet could have a massive impact on our
moods and mental stability.

~~~
rudolf0
I agree; this article is a little misleading. Any substance that rapidly
releases serotonin will definitely make you feel happy, if you're not already
tolerant.

It's obviously more complex than just being "the happy neurotransmitter", but
it is tied to general mood.

~~~
tachyonbeam
It is tied to mood, the reason it's more complicated though is that there are
many clusters of neuron in the brain which use serotonin to communicate. There
are 14 known serotonin receptor subtypes
([https://en.wikipedia.org/wiki/5-HT_receptor#Subtypes](https://en.wikipedia.org/wiki/5-HT_receptor#Subtypes)).
Psychedelic drugs (mushrooms, LSD, etc) typically act on 5-HT2a receptors.
Serotonin is involved in perceptual filtering, hence why fractal patterns and
hallucinations can occur when 5-HT2a is triggered.

I would actually say that there's a more obvious link between dopamine and
mood than serotonin. Dopamine releasers (amphetamines, meth, ritalin, cocaine)
produce an immediate uplifting and confidence-boosting effect. MDMA doesn't
just release serotonin, it also releases dopamine. The serotonin release from
MDMA is responsible for its powerful anti-anxiety effect. It's believed that
the "loved up" feeling from that drug is due to an indirect action of
serotonin which eventually produce oxytocin release.

