Resources for learning about The History of Serotonin

[dlind]

wanted to share a couple of books I’ve come across that helped me understand serotonin

"You can't understand the other things that I'm working on unless you know where serotonin fits in. To understand unsaturated fatty acids vs. saturated, you have to understand estrogen and serotonin, and to understand thyroid, you have to understand all of those." —Ray Peat

Serotonin’s role in the carcinoid syndrome has been mentioned by Georgi and others. It was found that carcinoid tumors produced serotonin, causing symptoms like diarrhea and flushing.

If you’re interested in learning about the carcinoid syndrome and its relationship to serotonin, Albert Sjoerdsma’s daughter Ann has written a detailed biography of her father titled, “Starting with Serotonin”

In the late 50s, Albert Sjoerdsma and Sydney Udenfriend measured the urinary metabolite of serotonin—5-hydroxyindoleacetic acid, or 5-HIAA—in carcinoid patients through a chromatographic assay. Their findings indicated secretion of serotonin by carcinoid tumors. This elevated production of serotonin created symptoms like flushing, asthma, and intestinal hypermotility.

Another excellent book concerning serotonin—particularly on the development of the serotonin theory of depression—is “A Short History of Serotonin.” The book begins in 1868 with the discovery [by two German scientists] that coagulated blood produces increased vascular tone, and concludes with serotonin becoming a household name [in the late eighties] amid the marketing of Prozac.

These two reads have helped me put serotonin in context. I’ve come to a deeper understanding in learning about the early experiments surrounding serotonin. I recommend both books as they contain many interesting references and anecdotes.

 

[TucsonJJ]

wanted to share a couple of books I’ve come across that helped me understand serotonin

"You can't understand the other things that I'm working on unless you know where serotonin fits in. To understand unsaturated fatty acids vs. saturated, you have to understand estrogen and serotonin, and to understand thyroid, you have to understand all of those." —Ray Peat

Serotonin’s role in the carcinoid syndrome has been mentioned by Georgi and others. It was found that carcinoid tumors produced serotonin, causing symptoms like diarrhea and flushing.

If you’re interested in learning about the carcinoid syndrome and its relationship to serotonin, Albert Sjoerdsma’s daughter Ann has written a detailed biography of her father titled, “Starting with Serotonin”

In the late 50s, Albert Sjoerdsma and Sydney Udenfriend measured the urinary metabolite of serotonin—5-hydroxyindoleacetic acid, or 5-HIAA—in carcinoid patients through a chromatographic assay. Their findings indicated secretion of serotonin by carcinoid tumors. This elevated production of serotonin created symptoms like flushing, asthma, and intestinal hypermotility.

Another excellent book concerning serotonin—particularly on the development of the serotonin theory of depression—is “A Short History of Serotonin.” The book begins in 1868 with the discovery [by two German scientists] that coagulated blood produces increased vascular tone, and concludes with serotonin becoming a household name [in the late eighties] amid the marketing of Prozac.

These two reads have helped me put serotonin in context. I’ve come to a deeper understanding in learning about the early experiments surrounding serotonin. I recommend both books as they contain many interesting references and anecdotes.

Interesting... does it explain how millions could do so well on SSRIs, often for 20+ years?
I'm not being a wise-guy... I really want to understand this.
G. Dinkov loves Methylene blue, it is a serotonin agonist. So is chlorpheniramine, which I take and it is great stuff...

 

[dlind]

Interesting... does it explain how millions could do so well on SSRIs, often for 20+ years?
I'm not being a wise-guy... I really want to understand this.
G. Dinkov loves Methylene blue, it is a serotonin agonist. So is chlorpheniramine, which I take and it is great stuff...

Methylene blue isn’t a serotonin agonist, it’s a monoamine oxidase inhibitor (MAOI)—monoamine oxidase is the enzyme that degrades neurotransmitters—and Methylene blue only inhibits monoamine oxidase at a high dose—you’d have to take at least 50mg—probably more—to get inhibition of MAO. Typically the dose of Methylene blue is half-a-milligram per drop, so you’d have to take 100 drops.

And chlorpheniramine isn’t a serotonin agonist. An agonist binds to the receptor and mimics the action of the transmitter substance. Chlorpheniramine is an antihistamine that functions as a weak serotonin re-uptake inhibitor. The book [A Short History of Serotonin] does cover the discovery that diphenhydramine (one of the most popular OTC antihistamines) inhibits the reuptake of serotonin. This discovery is used to formulate structural analogs of diphenhydramine that inhibit the reuptake of serotonin.

The text doesn’t argue against the use of SSRIs, it simply gives the history of their development.

 

[dlind]

Interesting... does it explain how millions could do so well on SSRIs, often for 20+ years?
I'm not being a wise-guy... I really want to understand this.

Within a limited therapeutic range, the SSRIs might be useful. Their pharmacological effect can diminish emotional responsiveness and reduce irritated reactivity.

If raising serotonin levels reduces irritability, it’s likely that apathy will be increased, and there’s a body of literature that suggests dose-related apathy may occur in persons treated with SSRIs.

Patients on SSRIs often experience less irritation, less care about others’ feelings, inability to feel sadness, lack of creativity, lack of surprise or anger, an inability to express their feelings, and lack of interest in sex.

If a person is in a situation where they’re overwhelmed and they want to reduce their metabolism and be emotionally blunted, SSRIs might be one form of “treatment.”

 

[TucsonJJ]

Within a limited therapeutic range, the SSRIs might be useful. Their pharmacological effect can diminish emotional responsiveness and reduce irritated reactivity.

If raising serotonin levels reduces irritability, it’s likely that apathy will be increased, and there’s a body of literature that suggests dose-related apathy may occur in persons treated with SSRIs.

Patients on SSRIs often experience less irritation, less care about others’ feelings, inability to feel sadness, lack of creativity, lack of surprise or anger, an inability to express their feelings, and lack of interest in sex.

If a person is in a situation where they’re overwhelmed and they want to reduce their metabolism and be emotionally blunted, SSRIs might be one form of “treatment.”

I found that to be the case years ago when I tried Celexa. But reviews on Drugs.com indicate that many do not feel the negative sides you listed... many find SSRI drugs to be "life-changing" to the good and that they bought back the enjoyment of life again...
I would not take a SSRI again, but might consider a fairly unique AD called Nefazodone... I think it functions much differently and doesn't effect serotonin nearly as much... I guess it blew up a few livers, but mostly in overweight boozers...
For now. a little nightly low-dose weed works well for me, but I do worry about it's hormonal effects and take some natural AIs to try to minimize this, like aspirin, K2 and/or E. I also just started taking low-dose Enclomiphene to boost my T levels... so far, no sides... I can't do TRT again...

 

[TucsonJJ]

Methylene blue isn’t a serotonin agonist, it’s a monoamine oxidase inhibitor (MAOI)—monoamine oxidase is the enzyme that degrades neurotransmitters—and Methylene blue only inhibits monoamine oxidase at a high dose—you’d have to take at least 50mg—probably more—to get inhibition of MAO. Typically the dose of Methylene blue is half-a-milligram per drop, so you’d have to take 100 drops.

And chlorpheniramine isn’t a serotonin agonist. An agonist binds to the receptor and mimics the action of the transmitter substance. Chlorpheniramine is an antihistamine that functions as a weak serotonin re-uptake inhibitor. The book [A Short History of Serotonin] does cover the discovery that diphenhydramine (one of the most popular OTC antihistamines) inhibits the reuptake of serotonin. This discovery is used to formulate structural analogs of diphenhydramine that inhibit the reuptake of serotonin.

The text doesn’t argue against the use of SSRIs, it simply gives the history of their development.

thanks for the info... my knowledge was lacking...
I did not find MB at doses up to 15mg to be noticeably effective, perhaps it was improving things anyway?
Great, I will continue taking chlorpheniramine and not worry about it... I only take 2mg in the afternoon and 2-4mg in the evenings...
BTW: Are YOU anti-serotonin as most Peaters are?

 

[dlind]

BTW: Are YOU anti-serotonin as most Peaters are?

Serotonin's actions in the brain are not yet completely understood, and given its diversity of functions, I'd be careful about the conclusions you draw. Arbitrarily raising levels can easily disrupt a tightly regulated system.

"Alterations in the transport, metabolism, storage, release, or postsynaptic activity of serotonin (5-HT) attend the administration of many drugs that influence functions mediated by the central nervous system (CNS). Moreover, considerable biochemical evidence links serotonergic mechanisms to the regulation of such diverse activities as sleep and body temperature, as well as to the pathophysiology of human ills ranging from schizophrenia and depression to epilepsy and parkinsonism."

"Nevertheless, the exact relationship of central indoleamines to any of these issues cannot be said to be clear in even a single instance."

From "Serotonin and central nervous system function." Annual review of pharmacology 13, no. 1 (1973): 181-197.

If you're interested in learning more, I'd encourage you to check out the books I referenced.

 

[rzero]

I can't find it now, but there was a recent study suggesting SSRIs may lower serotonin activity in net; that blocking the reuptake causes a compensatory decrease of serotonin production, resulting in lower brain serotonin than without the drug.

Not an endorsement of SSRIs, but definitely a testament to the very primitive state of neurobiology, despite what doctors and drug companies profess.

Edit: Haidut mentions it here: BOMBSHELL: Serotonin High in Depression, Not a “Happy” Chemical, Lowers Energy, Depression Self-Resolves – To Extract Knowledge from Matter

 

[dlind]

In 1989, there was a shooting at a printing facility (Standard Gravure) in Kentucky where the gunman killed his co-workers after taking Prozac (the first blockbuster SSRI).

What's telling is Eli Lilly's protocol adminstrator—Irwin Slater—was deposed after the victims' families sued Lilly, and he said the following about the antidepressive effect of Prozac:

[this was in 1994–Prozac had been on the market for seven years]

Attorney: What is your understanding in your conversations with Doctor Wong, Molloy and Fuller, the developers of this drug, as to why Fluoxetine Hydrochloride, Prozac, has an antidepressive effect on human beings?

Irwin Slater: I think it's because it prevents the reuptake of 5-hydroxytryptophan.

Attorney: Why is it that reduction of uptake of 5 hydroxy -- 5-HT produces an antidepressant effect in some humans?

Irwin Slater: I think it's because it increases the 5-HT levels in the brain.

Attorney: What is it about increased 5-HT levels in the brain that results in less depression?

Irwin Slater: I think you're asking me more than is really known about neuropharmacology at this stage in the history of the world.

If you're interested in reading the entire transcript you can find it here. The snippet I quoted is on page 349.

 

[dlind]

I can't find it now, but there was a recent study suggesting SSRIs may lower serotonin activity in net; that blocking the reuptake causes a compensatory decrease of serotonin production, resulting in lower brain serotonin than without the drug.

Not an endorsement of SSRIs, but definitely a testament to the very primitive state of neurobiology, despite what doctors and drug companies profess.

Edit: Haidut mentions it here: BOMBSHELL: Serotonin High in Depression, Not a “Happy” Chemical, Lowers Energy, Depression Self-Resolves – To Extract Knowledge from Matter

Another theory about how antidepressants work—proposed by Eric Stone at NYU—is that antidepressant drugs "mimic" the effects of chronic stress, inducing downregulation of β-adrenoceptors, which reduces the sensitivity of the stress system.

"Recent studies by Stone and Platt are relevant in this regard as these investigators have shown that the decrease in the density of β-adrenoceptors in brain is positively correlated with the degree of resistance to stress; that is, groups of rats with a greater degree of subsensitivity [reduced sensitivity] had a lesser degree of anorexia and stomach lesions following exposure to chronic stress. On the basis of these data, Stone has proposed that the response to antidepressant therapy is a form of adaptation to stress."

From the paper-
Stone, E. A., & Platt, J. E. (1982). Brain adrenergic receptors and resistance to stress. Brain Research, 237(2), 405-414.

"Subsensitivity can be induced pharmacologically by chronic treatment with antidepressant drugs or after repeated electroconvulsive shocks (ECS)"