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.
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.
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.
>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.
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.)
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-...
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."
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.
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"
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.
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.
Came here to pose the exact same question. I also always understood that one of the risks of repeated mdma intake is serotonin depletion. Also the effect where one feels like shit 1-3 days after an mdma trip is very real.
So while it is possible serotonin is not the happy chemical, it either does play a role (possibly or even likely if you ask me in combination with other chemicals) or else all other research so far has been very much wrong.
So, with its grain of salt, the Wikipedia article on MDMA begins the discussion with this statement:
> MDMA acts primarily as a presynaptic releasing agent of serotonin, norepinephrine, and dopamine, which arises from its activity at trace amine-associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2).
It goes on to state that MDMA acts as an inhibitor of VMAT2, which correlates to an increase of the neurotransmitters in the space near that receptor's neuron.
I think this means that it does operate on the brain by encouraging the release of more serotonin, norepinephrine and dopamine.
I don't know about frequent uses but I remember reading research paper which said that high doses are toxic, permanently damaging brain - so it's definitely not a good idea to take too many in too short time.
MDMA does not form a physical dependence. In fact, if you keep taking it, it will stop working altogether eventually, regardless of an increased dose.
There have been many bullshit studies with predetermined agendas and bad methodologies which have claimed that MDMA is neurotoxic. Whenever more responsible, un-biased studies are done, they usually show it is actually less "toxic" than alcohol.
It may not be a drug with risk of addiction, but MDMA is absolutely neurotoxic, even from a single dose. The neurotoxicity from a single standard dose is pretty negligible, and can be remediated with supplements, but frequent use (like once per week) will absolutely cause brain damage no matter what you do.
Here is a good overview of its different neurotoxicity factors from a well-regarded neuroscience researcher:
1. MDMA metabolizes into other chemicals which are prone to creating many reactive oxygen species, causing oxidative stress in different parts of the brain. This can be mitigated, partially, with anti-oxidant supplements.
2. MDMA directly harms and destroys receptors via serotonin, dopamine, and glutamate system via excitotoxicity. Infrequent use minimizes this. NMDA antagonists could also possibly help reduce some of the effects.
3. MDMA harms all parts of the brain by overheating it. Stay hydrated and prevent yourself from doing much physical activity in a hot area.
So, MDMA can be taken safely, but it is naturally neurotoxic, and must be treated with much respect and caution.
Other good advice for what supplements to take can be found at http://rollsafe.org
Actually nowhere near enough research has been done to understand what, if any, long-term damage frequent MDMA use can cause.
In the very short-term it is quite neurotoxic, and consuming too much can cause immediate problems. It looks like short-term problems can be minimised by taking a few weeks in between uses, and according to at least one study it looks like all damage can be undone by just a few months of abstience.
However there's really not enough data about lasting affects, if there are any, or about how frequency of use could impact your brain's outcome, or.... etc.
Anecdotally I've heard many stories of people using MDMA too often and "losing the magic", that it just stops giving them the effects they used to enjoy.
One other thing to note, you wrote "if you keep taking it, it will stop working altogether eventually, regardless of an increased dose" I'm no expert, and could well be corrected on this, but I suspect that is much more the case with the positive effects than with the downsides. For example MDMA is a drug known to have a "sweet spot" for most people, unlike many drugs (from booze to weed to cocaine) where different people build up different tolerances/preferences and therefore have a large range of doses, MDMA is generally thought to have quite a small range of good doses, after which increases will cause more/worse side affects without adding anything positive to the experience.
Well, if you can consume a decent dose of MDMA every day for all your life, like you can with alcohol (e.g. a glass or two of wine with your meal), without adverse effects, as tons of millions of people do with alcohol (e.g. in Spain, Greece, France, etc), then I don't see what's the concern.
You might be over-estimating how much alcohol the average French person drinks, or under-estimating the harm that results tot he regular drinkers.
"a glass or two of wine with your meal" "every day" is unequivocally harmful. It's a dangerous, pernicious myth (mostly promoted by alcohol companies) that daily alcohol is some how healthy.
A small number of French people drink very heavily. A bit less than 20% of the French population drinks wine daily. This contributes to the 49,000 or so who die of alcohol related disease each year.
>You might be over-estimating how much alcohol the average French person drinks, or under-estimating the harm that results tot he regular drinkers.
Well, I know how much people back in my village drink, and I probably underestimate it. As for effects, they merely live to 80-90 and still manage to work on the fields and such.
>"a glass or two of wine with your meal" "every day" is unequivocally harmful. It's a dangerous, pernicious myth (mostly promoted by alcohol companies) that daily alcohol is some how healthy.
Actually daily alcohol has been the norm for very long living populations, including this famed one, which I've met and seen personally:
>A small number of French people drink very heavily. A bit less than 20% of the French population drinks wine daily. This contributes to the 49,000 or so who die of alcohol related disease each year.
While that's true, that has to do more with the economy and modern trends (sodas etc). Historically it has been a much different picture:
"France's average wine consumption fall from 160 litres per adult, per year in 1965 to 57 litres in 2010, roughly the equivalent of a drop from three glasses to one glass per person, per day"
A lot of the fear about alcohol in the US comes from the fact that people are not properly taught to handle it (as something you drink with company, accompanying a meal, enjoying slowly etc), and use it in moderation from a young age (heck, the drinking age is 21 years olds), and instead use it in excess as some kind of recreation/pain killer/etc combo. Very few people at 19-21 in Europe (and especially regions like Spain, France, Italy, etc) would ever do the kind of BS stunts an American college student would do with beer and alcohol. (Though protestant and Northern countries tend to fare worse in this cultural aspect).
To quote:
"Comparing patterns of alcohol consumption between the United States and the majority of European countries, for example, reveals an interesting trend. In the U.S., the nation with one of the highest binge drinking rates worldwide, people tend to abuse alcohol. In Europe, by contrast, more people enjoy drinking alcohol without binge drinking because leisurely drinking is an important part of social interaction."
Well, one who is good at nitpicking should also be able to find links for the original papers in the articles -- as well as numerous others.
And if we're to nitpick, I'll have to say that at least I linked to "Telegraph and Reuters" whereas you didn't link to any source at all for your statements.
Did you categorize your depression into existential, situational or biochemical origin ? Would that have make sense in your case and could anti-depressants target a specific kind ?
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.
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.
PSA for people to be careful with 5-HTP, it can be dangerous to stack with various prescription medications and if you're taking it OTC you need to remember to disclose it to your doctor
Also, do NOT mix 5-HTP with St-John's Wort (don't mix St-John's Wort with anything, really.).
You may want to look up L-Tryptophan instead of 5-HTP. From my understanding (I am no doctor or scientist, but I do research what I put in my body), here is the order your body synthesize Serotonin: Tryptophan > 5-HTP > Serotonin > Melatonin. You may want to start with the Tryptophan itself. However, since taking 5-HTP, I have no interest in trying this out or taking any more of those supplements because I am feeling well now.
It's also recommended to take EGCG (green tea extract) along with 5-HTP to keep your gut from absorbing the supplement and producing Serotonin there instead of in the brain. (It could possibly lead to heart valve failure if you don't!)
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)
"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...)
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.
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.
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.
I'm not an alternative medicine fanatic, but neither am I someone who thinks that Big Pharma is nothing but an evil conspiracy, but I suspect at the end of the day, these things don't get a lot of attention because there's no "miracle drug" that can be patented and sold for billions.
They fall outside the jurisdiction of the FDA (whether they should or not is debatable), but I wouldn't write any of these items off just because they are marketed as supplements.
I think the best we can say is that we don't know enough about them and their effects. Look at how often the "eat X, it's good for you"/"don't eat X, it's bad for you"/"X has no significant effect" articles we see... often where X is the same thing in different categories.
It must depend on where you live and what kind of stores sell those supplements around you.
I purchased this bottle of 5-HTP at a pharmacy in the health supplements aisle next to vitamins and other products such as melatonin. At this pharmacy chain, this aisle is as important big and prominent as any regular medecine aisle. If you ask for over the counter medecine, there are chances the pharmacist will refer you to this very aisle (melatonin for sleep, etc.)
>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 problem is lots of the core science behind brain chemistry is sort of bogus, non reproducible stuff. And a lot of it is sponsored by pharma companies who have an extra motivation for getting (and showing) only the "good" results.
Did you take it daily for 2 weeks and/or are you certain you have issues with your Serotonin? Also, did you try taking it with green tea extracts to make sure most the 5-HTP is going to your brain and not your gut?
Personally, ever since it did have an effect and improved my mood, I can't notice any effects from it.
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.
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.
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
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.
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.
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.
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
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.
That's very interesting, I've never heard of that. Apparently it's a tricyclic, but doesn't have the same side effects that have caused most tricyclics to fall out of use. Never approved in the US, either, though current research suggests it works in different ways than the most common drugs.
I'm hopeful that as drugs unrelated to seratonin, norepinephrine, and dopamine start to show promise with depression, that we'll have a better picture of what's going on in the brain when people get depressed. IMO one of the missing pieces in severe depression treatment is what to do in the weeks it takes medications to take effect, if they even do; the current strategy seems to be "wait it out and if they're at risk of hurting themselves put them in a rubber room."
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.
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.
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).
This paragraph is rather inconsistent. The first sentence talks about the issue being one disorder rather than another, then supports that with a study finding that both are components.
It seems like a lot of people use that study as an argument for ignoring the part they're not interested in, rather than concluding that both components should be treated.
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.
> "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.
You need to be careful with the pill holiday thing. When I was taking venlafaxine, the withdrawl happened very fast and was miserable... if I missed two days I was in trouble.
My "discontinuation syndrome" was coming off desvenlafaxine. My access to it was suddenly taken away so I had no choice but to sit through the brain zaps for probably a week or two. You can't be sure how long it's going to last and that shit is as unpleasant as it gets.
This is why you need to taper off the drugs over 4 weeks. If it takes 4 weeks to start working, it makes sense it should take your brain the same amount of time to work properly without them.
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.
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.
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). 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.
>doesn't necessarily stimulate any sort of direct pleasurable feeling as people often infer.
Dopamine is very complex and acts on different receptors to achieve varying effects, but a sudden spike in dopamine concentration in many parts of the brain, like the nucleus accumbens, will usually result in a pleasurable feeling. This can be seen in people with dopamine-related disorders, like bipolar, and dopamine-releasing substances like amphetamine.
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.