The High Serotonin Personality

[Tom K]

Ridiculous. Is there any behavior not categorized under the list initially provided? fMRI of brain structure as related to behavior has dispelled many of what was presented in the list of behaviors. The architecture of the brain has a greater influence than the behavioralists admit. Can behavior change despite structural predisposition? Of course. But a persons' tendencies have been demonstrated to be more structural when fMRI research was employed to identify similarities among mammals, including we homo sapiens.

 

[Alpha]

I really don't like this reductionism.

Serotonin levels vary widely, as does every other hormone or neurotransmitter, depending on the tissue in question, and their effects are quite different depending on where they manifest, and the densities of their respective receptors.

Just felt like pointing it out.

 

[Hans]

I still believe these guys had the right general idea: Serotonin and brain function: a tale of two receptors

5-HT2A gets a lot of excess blame through correlation and sketchy experiments, and probably received some blame that belongs to 5-HT2C. The more I looked into it the clearer it was there are serious problems in the serotonin research, to the point it's almost impossible to rely on any of it, e.g. a number of aging research is now half-useless because the prime 5-HT1A agonist in experiments turned out to affect 5-HT7: 8-OH-DPAT - Wikipedia . There are so many contradictions in the experiments, and major species differences. Look at this crap: Serotonin 1A Agonism Decreases Affiliative Behavior in Pair-Bonded Titi Monkeys (2017). Wouldn't that be fantastic information? Oops except right in the discussion they write they're perfectly aware of the problem, they just... chose to ignore it. "Future work should utilize pharmacological agents with more specific activity, or concurrently block activity at 5-HT7 receptors to more clearly elucidate the mechanism of action responsible for changes to behavior." -> Why didn't you do that?! You had all the time in the world!!! 5-HT7 is a significant drug target.

By and large serotonin appears to be the "perceived threat" molecule: Reconciling the role of serotonin in behavioral inhibition and aversion: acute tryptophan depletion abolishes punishment-induced inhibition in humans This is generally the case outside the brain as well, so it's fairly consistent.

A lot of the "serotonin personalities" are probably greatly affected by the Dynorphin system (though it veers more toward PTSD territory). Serotonin (in the brain) works via prediction, while dynorphin (closely tied to CRH at the HPA, both ways) signals on the actual negative outcomes such as pain and failure, while instilling (and later extinguishing) fear memories. Acute effects of dynorphin are feeling like death, whereas acute effects of serotonin actually feel good (to deal with threats), if you go by the predominant receptors and common wirings. Long-term is a different story.

In other words there is a good part of it that is probably mediated by the dynorphin system, and although there isn't enough deep research on their connection, it stands to reason the dynorphin system may help set up the serotonin circuits. It will be cool to find out how the research connects them in the future (or unless I missed something), and contributes to all this.

In terms of "negative" social behavior, well I'm sure most know but it was unsaid that there is a strong role for both oxytocin and vasopressin, they may mediate the bulk of it, besides dopamine.

Kynurenine pathway is more directly responsible for energy regulation, and thus feelings of fatigue; dynorphin and serotonin work indirectly on energy regulation by inhibiting participation and reflection on energy-expensive activities. But as it's been beaten to death on this forum, low energy alone (thus kynurenine dysfunction alone) will lead to irritated personalities.

Gonna stop and click Post Reply cause I forgot where I was going with this.

Thanks for posting this. I agree, serotonin research is really sketchy atm, but there is direct proof of how pro-serotonin drugs influence behavior. There are so many interactions between hormones and neurotransmitters, which makes it very complicated.

 

[Hans]

What else can resensitize the 1A receptor?

Estrogen, cortisol and serotonin decrease the 5-HT1A receptor, so keeping those low will be very helpful in increasing 5-HT1A sensitivity.

 

[Runenight201]

Ridiculous. Is there any behavior not categorized under the list initially provided? fMRI of brain structure as related to behavior has dispelled many of what was presented in the list of behaviors. The architecture of the brain has a greater influence than the behavioralists admit. Can behavior change despite structural predisposition? Of course. But a persons' tendencies have been demonstrated to be more structural when fMRI research was employed to identify similarities among mammals, including we homo sapiens.

Im interested, could you please refer me to some reading?

 

[Hans]

Well, here's some food for thought:
Serotonin stimulates hypothalamic mRNA expression and local release of neurohypophysial peptides. - PubMed - NCBI
https://www.researchgate.net/public...sticular_Response_to_the_Presence_of_a_Female

Don't have time to go into those, which may give yet different ideas than what I'm about to write: I think the thing to notice is that 5-HT2 (either A or C, there was some disagreement in studies) are solely responsible among the 5-HT receptors for Vasopressin release; 5-HT1a can only release Oxytocin. According to all the shitty studies, anyway.

Don't remember where I read the bulk of this, so good old wikipedia to the rescue:
Sexual motivation and hormones - Wikipedia


Also it is possible (I think likely, or at least circumstantially true) 5-HT2a increases testosterone a little, though again the studies conflicted (I don't know if it was resolved somewhere by someone). But since 5-HT2a is even found outside the brain (it's inside the brain that was less clear to me), you could get issues from something such as this, since presumably taking ashwaganda systemically is unlikely to discriminate unless it just doesn't get into the tissues:
Ketanserin, an antagonist of 5-HT2A receptor of serotonin, inhibits testosterone secretion by rat Leydig cells in vitro. - PubMed - NCBI

For 5-HT1a itself, it's possibly a reason people like fish oil's effects, besides the inflammation thing:
The role of 5-HT₁A receptors in fish oil-mediated increased BDNF expression in the rat hippocampus and cortex: a possible antidepressant mechanism. - PubMed - NCBI
Omega-3 fatty acid deficient male rats exhibit abnormal behavioral activation in the forced swim test following chronic fluoxetine treatment: assoc... - PubMed - NCBI

Don't particularly recommend unless you've hit rock bottom

Keep in mind in all this the 5-HT1a receptor is possibly severely confused with 5-HT7 (this gives the hypothermia). That's about all I can write today.

High serotonin just kills my libido dead.

 

[Cirion]

High serotonin just kills my libido dead.

Same here.

Granted "High Serotonin" can be a little subjective as implied in some posts here, and not everyone will have all the symptoms posted (although someone who is particularly unwell will tend to check more boxes, which I can personally attest to).

 

[Terma]

my familiarity with neurochemistry is non-existent, but doesn't ashwagandha increase 5-H2a receptors and thereby increase testosterone? or is this what you're saying? to be honest, i don't understand how ashwagandha could have caused these issues, but it seems to have done so, regardless... the brain should have gone back to normal by now, but it undoubtedly hasn't. the symptoms fit those of elevated serotonin, too, but i understand that it's not so black-and-white

It's next to impossible to know what the herb did exactly on your own - you said 3 years? - without research-level diagnostics. There are too many variables, and Ash is a big one (consider that the study which measured its effects in rats modeled the experiment after typical SSRI progression, yet Ash is known to increase thyroid T3 and have neuroprotective effects...). Some 5-HT2a effects may still be confounded with 5-HT2c, and their effects have even been confused with 5-HT1x (direct and indirect). The very model of up/downregulation everyone assumes (even studies) is known to be unreliable for some receptors such as 5-HT2a and some acetylcholine ones, depending on the drug, supposedly due to different binding domains. Then there's likely species differences in behavior, serotonin is product of evolution. Ashwaganda might be doing something completely different than expected, effects in its studies were inferred indirectly. Even if it did do exactly what everyone assumes, you could have a progression and complications in several parts - perhaps most likely out of all these. So as we're doing, the most successful (still failing) estimation is to go by symptoms of the downstream hormones thought to be promoted by serotonin, since that's its primary action, assuming you can get one or two of those right.

If you had excessive 5-HT2c stimulation you'd probably be anxious and submissive frequently, rather than anhedonic and bored, so I kinda doubt that one. If you had none at all you might have a distorted circadian rhythm (but again, 5-HT7 crashes the party). It's been thought to increase prolactin. Then there's vasopressin. Summarized conveniently (Warning: Wikipedia again): 5-HT2C receptor - Wikipedia: "Stimulation of 5-HT2C receptors leads to increase of corticotropin releasing hormone (CRH) and vasopressin mRNA in the paraventricular nucleus and proopiomelanocortin in the anterior pituitary lobe. In rats, restraint stress (which can produce depressive symptoms if being chronic) induces secretion of prolactin, ACTH, vasopressin and oxytocin which is partially mediated via 5-HT2C receptor. Responses during such conditions as dehydration or haemorrhage causes the release oxytocin via serotonergic response that is partly mediated via 5-HT2C. In addition, peripheral release of vasopressin involves serotonergic response which is partially mediated via 5-HT2C."

This was already said but if 5-HT2a were being actively stimulated you would likely notice something easily confused with "positive", such as dopamine (as OP mentions), test, faster thinking, because it's generally the "nootropic" serotonin receptor - unless it was drowned out by dynorphin/other...

Maybe get cortisol tested by a good endo if no one suggested that yet. If there were a real "stress loop" somewhere cortisol would be involved. Anhedonia could be mediated in a PTSD-like fashion with downregulation of the CRH feedback receptors due to high cortisol (could be triggered or sustained by serotonin), leading to high CRH. In turn this increases dynorphin which proactively kills off dopamine effectively (as opposed to the generic "serotonin antagonizes dopamine" mantra). In that case CRH+dynorphin+cortisol are the persistent culprits. There are even studies showing cortisol increasing serotonin (afterward, consider the possibility dynorphin theoretically helps modulate the serotonin circuits; it is known to acutely actually lower serotonin release in some areas - which actually makes sense - though receptors/wiring remains a mystery?). In other words the original trigger could disappear once the loop sets in. I'm not sure to what degree this could explain PSSD, the KOR fear memory concept gives it a more PTSD flair. All I can do is give hints. However I agree with something the other guy implied: some of these may not be true stress "loops" at all but be localized in different brain areas/circuits so they only "loop" with the flawed systemic administration of drugs, which is almost like artificially linking brain areas. Moving on...

I think it's possible for cortisol to lower vasopressin as well, but the reference was in a book.

Yet another complication: Cortisol has been recorded as desensitizing the 5-HT1a autoreceptors in its serotonin-promoting effect (in brain), just like an SSRI, though this is full of assumptions too: Sci-Hub | Repeated cortisol administration attenuates the EEG response to buspirone in healthy volunteers: evidence for desensitization of the 5-HT1 A autoreceptor. Journal of Psychopharmacology, 21(8), 826–832 | 10.1177/0269881107078292. Unlike them it's not (did not see evidence that it was, correct me if wrong in anything here, this is hard) a specific 5-HT receptor modulator. Yet, high-stress states are generally assumed to be pro-5-HT2a. But here you have a situation promoting higher serotonin release while supposedly not downregulating the 5-HT2a receptor (perhaps it increases SERT to compensate?)... So what will Ashwagandha do you think, since it well enough lowers cortisol? I hope I confused you well enough.

The rest of my observations are anecdotal, but it's worth noting that the entire post-finasteride PSSD userbase that was here moved to a forum dedicated to balancing minerals. If that doesn't conjure up pictures of vasopressin I don't know what will. Also RU486 should become familiar to you in short order due to these: Cortisol-mediated downregulation of the serotonin 1A receptor subtype in the Gulf toadfish, Opsanus beta. - PubMed - NCBI. I suppose you could try Lisuride if you haven't (take only in morning). I can't remember if it was a proven 5-HT2c agonist (on top of the dopamine) but subjectively it felt quite peculiar to me. If you're about to kill yourself, at least give yourself a break on a weekend or two a month (never daily) with MDMA or some high-dose phenibut (worked up to 3g+). Phenibut (in high doses only) dramatically increases my fluid retention while doubling aspects of my sex drive, and I'm not even looking for it, even though they (known for MDMA, for phen I've assumed) increase cortisol and/or serotonin signaling at those doses one way or another.

As a disclaimer, I haven't read every single Ashwagandha study in existence, so I'm sure there are better experts on that particular drug and so forth, probably someone someday will find errors in this post.

Thanks for posting this. I agree, serotonin research is really sketchy atm, but there is direct proof of how pro-serotonin drugs influence behavior. There are so many interactions between hormones and neurotransmitters, which makes it very complicated.

Yeah, it's harder to figure out beyond most pathways I've tried to follow, I can't do this every day, and for the longest time I missed the simplest things. It's just slowly been forming a picture in my head over the last year, and in large thanks to that tale of two receptors study which is roughly your general idea which prompted those posts (then drifted as usual).

 

[Hans]

High serotonin causes "enlightenment" experiences.
Serotonergic and tryptaminergic overstimulation on refeeding implicated in "enlightenment" experiences. - PubMed - NCBI
"The classic "enlightenment" experience is that of Siddhārtha Gautama (a.k.a. Buddha) who fasted and meditated intensely for years but failed to attain his goal of "enlightenment." He gave up his fast, ate rice pudding, and immediately meditated again, whereupon he attained "enlightenment." The hypothesis is that this altered state was a symptom of refeeding after prolonged starvation resulting from the combination of monoamine oxidase (MAO) inhibition followed by tryptophan and carbohydrate intake. Intense fasting inhibited Gautama's MAO activity; eating rice pudding constituted an intake of dietary tryptophan with carbohydrates. Carbohydrates trigger insulin release, which increases unbound tryptophan while reducing levels of competing amino acids at the blood-brain barrier. These effects allow significant amounts of tryptophan into the brain, where it converts into serotonin. Without MAO, serotonin does not degrade, and methyl-transferases convert excess tryptophan and serotonin into endogenous psychoactive tryptamines. The endogenous serotonin and tryptamines cause altered mental states. The absence of psychoactive substances and the prolonged fasting gives this experience its perceived spiritual power. Subjects may have no option but to assume that their experiences were due to either divine intervention or to values and techniques that took many years of hard work to acquire."

Looks like serotonin promotes the behaviour of people that think they have all the answers because they feel so enlightened.

 

[Cirion]

People like to think that how they are is just how they are and that's one reason why people just go with the flow and not try to change. True there are some unique character traits that every human has, to a degree.

But like it or not, 90% of who we are is literally the state of our hormones at any given point in time. I think this is only really apparent to those like myself, Hans and others here who have experienced both unhealth and true health. We as humans rarely believe something we haven't seen, touched, or otherwise experienced for ourselves. It's one of our weaknesses and why history often repeats itself.

When I used to post on anabolic men forums there was this guy that said he went from just an every day grunt to a CEO of a company from optimizing his hormones.

Speaking of CEO's, the CEO of the company I work for, you can literally feel the health exuding from him - he looks fantastic. I can tell just by looking at him that he makes his health a priority.

I think of optimizing your hormones as "unlocking your true potential". It was in you all along, but serotonin and lack of dopamine etc was inhibiting you.

 

[Hans]

People like to think that how they are is just how they are and that's one reason why people just go with the flow and not try to change. True there are some unique character traits that every human has, to a degree.

But like it or not, 90% of who we are is literally the state of our hormones at any given point in time. I think this is only really apparent to those like myself, Hans and others here who have experienced both unhealth and true health.

When I used to post on anabolic men forums there was this guy that said he went from just an every day grunt to a CEO of a company from optimizing his hormones.

Speaking of CEO's, the CEO of the company I work for, you can literally feel the health exuding from him - he looks fantastic. I can tell just by looking at him that he makes his health a priority.

I think of optimizing your hormones as "unlocking your true potential". It was in you all along, but serotonin and lack of dopamine etc was inhibiting you.

Yeah, I also don't see serotonin as the hormone that will take you forward in life, because it's elevated as a coping mechanism, to resolve is problem. And as long as there is a problem, serotonin will be high, and the organism can't/or at least struggles greatly to excel until the problem has been fixed. And then if serotonin is still elevated post problem, there is a maladaptive state that needs to be fixed.

 

[bboone]

This was already said but if 5-HT2a were being actively stimulated you would likely notice something easily confused with "positive", such as dopamine (as OP mentions), test, faster thinking, because it's generally the "nootropic" serotonin receptor - unless it was drowned out by dynorphin/other...

wow, thanks for the detailed reply. yeah, this is what seems so strange to me. my health in every other way is leagues better than it used to be. my testosterone is higher and i have less traits that would suggest high estrogen. this isn't necessarily due to the ashwagandha, but i'm certain it didn't negatively affect it. my ability to concentrate is far better than it has ever been, my recall is sharper and my intellectual capacity is greater. i literally never feel stressed and i haven't been anxious in years (i was quite anxious during my late teens due to extreme bouts of paranoia, whose origin actually justified it). i'm not as quick as i was earlier to put all my negative symptoms on the ashwagandha usage, as i set up the perfect storm for myself, with a high-stress environment, severe weight loss (intentional) and two major traumatic episodes.

couple this with frequent recreational drug use, and ashwagandha may not seem as big of an antagonist as i initially assumed. however, the "trouble" i was referring to started shortly after i quit ashwagandha, and i also react very negatively to zinc and rhodiola, which leads me to believe that there has been some excessive meddling with a serotonin receptor or two... anyway, to conclude the diary entry, thanks again for the comprehensive reply. there are more aspects than i had initially thought. i've also gone idle for about a year now with little progress in my academic "career", so that may have created a problem state, which hans described above. not enough successes and too little sense of self-realization. the state may not be entirely maladaptive after all lol

 

[Terma]

@bboone
I nearly forgot: if you have PSSD you might want to make sure you haven't destroyed your histamine levels somehow. Histamine is important for libido, there is a review on pubmed I forgot the search terms.

In that respect a cyproheptadine trial would almost be an interesting tool, although it's so broad-acting I'm not sure to what extent you can infer anything with it.

 

[bboone]

@bboone
I nearly forgot: if you have PSSD you might want to make sure you haven't destroyed your histamine levels somehow. Histamine is important for libido, there is a review on pubmed I forgot the search terms.

In that respect a cyproheptadine trial would almost be an interesting tool, although it's so broad-acting I'm not sure to what extent you can infer anything with it.

i don't think i have PSSD. i only exhibited one very mild variant of one PSSD symptom. i can still get an erection whenever i want and maintain it for however long i may feel like it, and my orgasms are rewarding. the major shift is that i pretty much lost the "drive" to seek out sexual encounters, and the pleasure of satisfying the urge which was previously there is pretty much gone. however, it varies. i also said i feel less pleasure from entertainment etc, but i wouldn't really associate that with PSSD. as far as i understand, SSRIs are much more potent than ashwagandha could ever be. i'm going to attempt to get a battery of blood tests done so that i have some numbers at hand

 

[Terma]

Oh okay. Yeah no problem, although I will say that going over serotonin research is - aptly - stressful. At least the Dynorphin system they can half-claim the research is in its infancy.

In that case you're a bit closer to me somewhat. I have no physically sex drive issues and I mostly landed on all the sex-related info incidentally. I suspect CRH/cortisol/dynorphins playing a part in my own issues, with serotonin kind of on the side (decided after going through like 6 supposed serotonin agonists/antagonists getting little of what I was looking for). Like you I don't have low test or high prolactin. But going on is pointless because the depth of my health issues distorts anything I can contribute in the n=1 sense.

 

[Runenight201]

High serotonin causes "enlightenment" experiences.
Serotonergic and tryptaminergic overstimulation on refeeding implicated in "enlightenment" experiences. - PubMed - NCBI
"The classic "enlightenment" experience is that of Siddhārtha Gautama (a.k.a. Buddha) who fasted and meditated intensely for years but failed to attain his goal of "enlightenment." He gave up his fast, ate rice pudding, and immediately meditated again, whereupon he attained "enlightenment." The hypothesis is that this altered state was a symptom of refeeding after prolonged starvation resulting from the combination of monoamine oxidase (MAO) inhibition followed by tryptophan and carbohydrate intake. Intense fasting inhibited Gautama's MAO activity; eating rice pudding constituted an intake of dietary tryptophan with carbohydrates. Carbohydrates trigger insulin release, which increases unbound tryptophan while reducing levels of competing amino acids at the blood-brain barrier. These effects allow significant amounts of tryptophan into the brain, where it converts into serotonin. Without MAO, serotonin does not degrade, and methyl-transferases convert excess tryptophan and serotonin into endogenous psychoactive tryptamines. The endogenous serotonin and tryptamines cause altered mental states. The absence of psychoactive substances and the prolonged fasting gives this experience its perceived spiritual power. Subjects may have no option but to assume that their experiences were due to either divine intervention or to values and techniques that took many years of hard work to acquire."

Looks like serotonin promotes the behaviour of people that think they have all the answers because they feel so enlightened.

I’ve often wondered if those who communicate with God have a biological state that is capturable and thus more easily replicable. I’m not too sure about that serotonin hypothesis, because those who claim to experience Divinity often do it in states of fasting and prayer.

I would consider the enlightened individual in the Buddhist sense to be undergoing the same type of conscious experience as the Christian communicating with God. Both are experiencing Divinity, they’re just explaining it though different cultural and linguistic lenses.

There certainly is a physiological/psychological state of consciousness that induces such divine episodes, and what the exact parameters surrounding these states I’m not sure are completely known.

I do know that people who are able to achieve such states usually don’t impose their will on others or are arrogant in any way shape or form. In fact, they are usually very humble, altruistic, empathetic, and passive. If these characteristics are attributed to high serotonin than I’d have to agree with another poster here about the serotonin reductionism being committed here.

 

[Hans]

I’ve often wondered if those who communicate with God have a biological state that is capturable and thus more easily replicable. I’m not too sure about that serotonin hypothesis, because those who claim to experience Divinity often do it in states of fasting and prayer.

I would consider the enlightened individual in the Buddhist sense to be undergoing the same type of conscious experience as the Christian communicating with God. Both are experiencing Divinity, they’re just explaining it though different cultural and linguistic lenses.

There certainly is a physiological/psychological state of consciousness that induces such divine episodes, and what the exact parameters surrounding these states I’m not sure are completely known.

I do know that people who are able to achieve such states usually don’t impose their will on others or are arrogant in any way shape or form. In fact, they are usually very humble, altruistic, empathetic, and passive. If these characteristics are attributed to high serotonin than I’d have to agree with another poster here about the serotonin reductionism being committed here.

There are two kinds of people that experience "elightenment". One is the true righteous believer that fasts and prays for a certain reason.

The other is the typical high serotonin person/psychopath that just gets "enlightened" and everyone has to listen to them because they are so spiritual and have all the answers for everyones life.

Like you say, the one is humble and doesn't force his believe, while the other is a narcissist that likes being in control and tell everyone the "truths" because they are so "spiritual" and "enlightened", yet when no one is looking, they do all the sins that they preach other people shouldn't do. Those people are one of the major reasons people hate Christianity.

 

[Cirion]

I have another explanation too - there is some stuff that connect spirituality to the physical world we don't fully understand yet. The "true righteous believer" as you put it, actually can to an extent, channel spiritual energy into their physical bodies, to some extent having positive effects both on hunger levels as well as positive hormonal levels. In this context, I believe its actually possible to maintain good hormone levels even while fasting. In this instance, the faster would NOT have high serotonin levels.

Maybe after all, "Man does not live on bread alone" (an infamous quote in the NT by Jesus). But yeah, nobody likes a hypocrite or someone who pushes their lifestyle on others especially when they're not living it themselves.

 

[Runenight201]

I have another explanation too - there is some stuff that connect spirituality to the physical world we don't fully understand yet. The "true righteous believer" as you put it, actually can to an extent, channel spiritual energy into their physical bodies, to some extent having positive effects both on hunger levels as well as positive hormonal levels. In this context, I believe its actually possible to maintain good hormone levels even while fasting. In this instance, the faster would NOT have high serotonin levels.

Maybe after all, "Man does not live on bread alone" (an infamous quote in the NT by Jesus). But yeah, nobody likes a hypocrite or someone who pushes their lifestyle on others especially when they're not living it themselves.

This is why I find spirituality so important. Ideally we would all be healthy when given the right diet, environment, lifestyle, etc... but to have all that go in your favor is historically a rarity and also isn’t always guaranteed moving forward in the future.

The properly developed spiritual life essentially guards against inopportune diet and environment, as seen by sages, saints, mystics, etc...many of whom eat an absolute horrid diet or live in terrible conditions, yet live in genuine joy and happiness due to their spiritual connection with Divinity.

I definitely would love to have that connection. As long as I have complete control over my diet and environment I’ve managed to set something up that works for me, but I’d love to have that freedom to let go some of that control and be able to maintain positive demeanor, energy, and sleep no matter where I go, what I eat, who I’m surrounded by, etc...

 

[Cirion]

Yeah to be honest my best health was when I was more in tune with my faith and more in fellowship with other like minded people. I've been slacking off lately. I think it will help me to try to get back into that. I still firmly believe being in tune with nutrition and environment is important too though, because I was feeling bad even with fellowship when my diet was bad.

Every piece of the puzzle matter. We must try to optimize all aspects as much as we can.