Serotonin Dominance And How To Deal

[Anonymous]

When I drink milk I now drink it with BCAA's. It definitely warms me up. It's pretty incredible.

 

[RPDiciple]

Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.

And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.

Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.

One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...

If you want to know the answer to this question, just read his papers. They explain.

What is your height and weight and activity level. What have you noticed since getting 200g of protein? in terms of benefits

 

[pyttsan]

Try Shilajit. Best I ever tried.
Panax Ginseng may work as well but personally I don't like its effects.

 

[BobbyDukes]

Panax Ginseng raises acetylcholine, nitric oxide, cortisol and, according to one paper, is a 5ht2a agonist (which I don't personally think is bad, as there is nothing more mind numbing than 5ht2a antagonism; story short, I've never come across one drug that boosts my mood, that operates as a 5hta antagonist; they are mostly all anti-psychotics for a reason).

Are you sure Panax is a Peaty herb, for this problem?

I used to take Panax, and always enjoyed taking it (despite it providing horrific anxiety). Since going Peat, however, I notice that the mostly beneficial effects are actually nothing but a stress reaction. It's mechanism works opposite to thyroid, if you consider the things it raises (that I mentioned above).

Try combining Panax with coffee, for fun. Weeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee.

As for Shilat, I've tried that too, and didn't really notice much. It lowers serotonin?

I've nothing personal against Chinese herbal medicine, or these 'revered' herbs. I just find it highly suspicious when I hear from Peat (96 interview 'thyroid') that literally millions of Chinese are hypothyroid. I guess that tells a story. Maybe they wouldn't need herbs, if they cut down on the lentils, beans, soy and oils.

 

[haidut]

Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.

And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.

Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.

One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...

This thread has a study shedding light on the mechanism of Prozac and other ssri's:

viewtopic.php?f=68&t=1964

Thanks! Though I find the linked evidence to be clearly insufficient to explain the SSRI issue.

Most SSRI's raise levels of allopregnanolone, which has undisputed antidepressant and neurogenesis effects. You can search Google for "Prozac allopregnanolone". However, it only happens after 2-4 weeks, which may explain why people are much more likely to commit suicide in the first 2 weeks of SSRI use when the only thing they do is raise serotonin. I posted a study recently where even big pharma said the theory is wrong and backwards - i.e. serotonin causes depression. In addition, fluoxetine (Prozac) is a 5-HT2 receptor antagonist, similar to mianserin and cyproheptadine btoh if which are known to be antidepressants. So, at least some of the SSRIs seem to be a mixed bag in terms of serotonin and also have desirable side effects on neurosteroids.

 

[TeslaFan]

I measured my serotonin 3 times since last year, including just recently. I noticed a dramatic drop with the last measurement, following 6 days on Azithromycin.

Blood serum serotonin measurements:
First: 216 ng/mL, in May 2014
Second: 199 ng/mL, in March 2015
Third (about two weeks after Azithromycin treatment): 107 ng/mL, June 2015.

 

[tara]

I just find it highly suspicious when I hear from Peat (96 interview 'thyroid') that literally millions of Chinese are hypothyroid. I guess that tells a story. Maybe they wouldn't need herbs, if they cut down on the lentils, beans, soy and oils.

That might do it.
Cut down enough from a minimal diet, and they might not need much of anything ever again.

 

[Makrosky]

Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.

And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.

Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.

One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...

If you want to know the answer to this question, just read his papers. They explain.

Sorry but no, they don't explain it consistently enough.

And it also doesn't explain why there are quite a few studies in pubmed alleviating depressive symptoms with l-tryptophan or 5-htp. There's also heaps of anecdotal evidence for that on naturopathic publications and schools, and hundreds of testimones with good results on internet forums and the like. I also experienced good benefits from it (5-htp) with myself and actually the complete opposite of what Peat claims happens (aggressiveness, learned helplessness, etc.).

Haidut has posted something very interesting related to Prozac and Pregnenolone, but that is strictly related to Prozac, not to serotonin or SSRIs in general.

 

[Makrosky]

Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.

And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.

Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.

One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...

This thread has a study shedding light on the mechanism of Prozac and other ssri's:

viewtopic.php?f=68&t=1964

Thanks! Though I find the linked evidence to be clearly insufficient to explain the SSRI issue.

Most SSRI's raise levels of allopregnanolone, which has undisputed antidepressant and neurogenesis effects. You can search Google for "Prozac allopregnanolone". However, it only happens after 2-4 weeks, which may explain why people are much more likely to commit suicide in the first 2 weeks of SSRI use when the only thing they do is raise serotonin. I posted a study recently where even big pharma said the theory is wrong and backwards - i.e. serotonin causes depression. In addition, fluoxetine (Prozac) is a 5-HT2 receptor antagonist, similar to mianserin and cyproheptadine btoh if which are known to be antidepressants. So, at least some of the SSRIs seem to be a mixed bag in terms of serotonin and also have desirable side effects on neurosteroids.

Thanks haidut!!! Very interesting info as always. I didn't know about the existence of allopreg. Apparently it's synthesized after progesterone, not pregnanolone itself.

I am interested in your views on why there's a mass of evidence in pubmed studies, clinical practice and anecdotal stories of direct serotonin precusors to alleviate or heal (while under treatment) depression and anxiety. I mean 5-HTP and L-Tryptophan.

I never found an explanation for that on RP's articles.

 

[Makrosky]

Panax Ginseng raises acetylcholine, nitric oxide, cortisol and, according to one paper, is a 5ht2a agonist (which I don't personally think is bad, as there is nothing more mind numbing than 5ht2a antagonism; story short, I've never come across one drug that boosts my mood, that operates as a 5hta antagonist; they are mostly all anti-psychotics for a reason).

Are you sure Panax is a Peaty herb, for this problem?

I used to take Panax, and always enjoyed taking it (despite it providing horrific anxiety). Since going Peat, however, I notice that the mostly beneficial effects are actually nothing but a stress reaction. It's mechanism works opposite to thyroid, if you consider the things it raises (that I mentioned above).

Try combining Panax with coffee, for fun. Weeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee.

As for Shilat, I've tried that too, and didn't really notice much. It lowers serotonin?

I've nothing personal against Chinese herbal medicine, or these 'revered' herbs. I just find it highly suspicious when I hear from Peat (96 interview 'thyroid') that literally millions of Chinese are hypothyroid. I guess that tells a story. Maybe they wouldn't need herbs, if they cut down on the lentils, beans, soy and oils.

Regarding the Panax issue : Chinese Medicine is a complex science. In TCM herbs are almost never given alone. Normally in formulas of 6-20 different herbs. Also, the one-sizefits-all approach is nonsense in TCM. The treatment is individualised for specific constitution and energetic imbalances. For one specific condition saturated fat will be bad, for others it will heal you. Some have to favour raw food, some avoid it completely. Same with exercise and with lots of other variables. It also takes into account emotional/social aspects.

If chinese people are physically different externally, why do you think their thyroids should operate on the same parameters than ours?

Ginger is one of the most revered medicines/foods in TCM and guess what? It's a serotonin antagonist.

There ara different approaches to good health.

 

[haidut]

Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.

And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.

Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.

One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...

If you want to know the answer to this question, just read his papers. They explain.

Sorry but no, they don't explain it consistently enough.

And it also doesn't explain why there are quite a few studies in pubmed alleviating depressive symptoms with l-tryptophan or 5-htp. There's also heaps of anecdotal evidence for that on naturopathic publications and schools, and hundreds of testimones with good results on internet forums and the like. I also experienced good benefits from it (5-htp) with myself and actually the complete opposite of what Peat claims happens (aggressiveness, learned helplessness, etc.).

Haidut has posted something very interesting related to Prozac and Pregnenolone, but that is strictly related to Prozac, not to serotonin or SSRIs in general.

I think Peat may not be entirely correct on the tryptophan angle. Tryptophan restriction extends lifespan and protects from disease due to the reduction in serotonin and other toxic tryptophan metabolites. However, there is limited evidence that tryptophan itself is bad for us except for its inhibition of thyroid hormone synthesis. However, the studies on tryptophan and thyroid were done in vitro AFAIK and do not take into account the systemic in vivo effects of tryptophan, which when taken all into account may be a net positive for some people ASSUMING we can prevent tryptophan from converting into bad stuff. For instance, the serotonin producing enzyme TPH is actually very powerfully inhibited by higher doses of tryptophan. So, in theory taking a high dose tryptophan (2g+) combined with niacinamide and vitamin B6 to block pathways for toxic tryptophan metabolism would give you a dopaminergic (mood) and metabolic boost. However, given that tryptophan metabolizes into primarily toxic stuff with the notable exception of niacin, I think we are better off not playing with it even though it may have some beneficial effects on its own.
For instance, virtually all cancers have extreme preference for quickly degrading tryptophan into one of its toxic metabolites and thus stimulating tumor growth. Virtually all cancer patients are thus tryptophan deficient and serotonin dominant due to this enhanced degradation. It is one of the possible mechanism explaining why cancer patients cannot metabolize protein properly or build muscle mass given that tryptophan is an essential amino acid.
There have been some very interesting studies in Russia on treating cancer with a combination of free amino acids including higher doses of tryptophan and giving the patients drugs that block the enzymes IDO, TDO and some other toxic metabolic pathways of tryptophan. The cancer patients started building muscle mass without even training, normal eating and weight were restored and depending on the type of cancer in some patients the cancer disappeared.
Btw, the positive effects of BCAA + tyrosine / phenylalanine come from reduction in tryptophan availability for conversion into serotonin, not blocking tryptophan absorption per se.

On a side but related note, one of the most important discussions we started in the forum was on the issue of protein metabolism and anabolism. As many of you know very well from personal experience, protein can be a hit or miss for many people and with aging we seem to need more protein to produce the same anabolic response. However, more protein may also mean more toxicity. This is no coincidence, as aging and disease like cancer are catabolic processes that inhibit the proper metabolism of protein. As an example, most people over age of 35 accumulate ammonia when eating protein. In healthier people this ammonia is kept at bay, but with hypothyroidism and aging or disease (which are really the same process anyways) ammonia builds up, as well as toxic metabolic byproducts of specific amino acids like methionine, cysteine and tryptophan. Some sources on the Internet claim that all protein except egg whites are net catabolic beyond a certain age. So, no matter how much protein one may eat one may end up doing more damage then good. Peat's solution is to increase metabolism and protein synthesis by taking thyroid, which is a proven and viable option to do so. However, another option is to supplement free amino acids in specific proportions. This way you can actually do perfectly well on as little as 30g of protein daily since it will be almost 100% anabolic, as opposed to the 30% anabolism of regular protein. Egg whites are claimed to be 60% anabolic and are a rich source of cystein and glycine, which combined raise glutathione lilke no other natural substance. I posted a study showing daily dose of 10g glycine and 10g cysteine restored glutathione in HIV patients and in some people arrested disease progression.

Note: I would like to give credit to forum member gbolduev who first alerted me to these aspects of tryptophan, protein metabolism, and its effects on health. He is one smart dude, but comes across as arrogant and since he does not like to use or read studies a lot of the stuff he says sounds like he made it up (i.e. stuff like 80% of people have high CO2 and the other 20% have low CO2). So, gbolduev, if you are reading this you should come back and rejoin the discussion. You have some very good (and provably correct) points, but just like you said that Peat is wrong sometimes, so are you, and so am I. So, maybe together we can build a bigger truth than each of our individual deluded selves

 

[HDD]

I observed my son go into depression from adding whey protein, melatonin, and then 5htp in approximately 2 weeks. The 5htp was the straw that broke the camel's back. It killed his appetite which lowered his metabolism. He first stopped leaving the house and then his bedroom. He became light and then noise sensitive. His appetite diminished. He became angry and severely depressed. I have never seen him this depressed. It was awful and frustrating since information online says that it helps anxiety and depression.

 

[haidut]

Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.

And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.

Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.

One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...

This thread has a study shedding light on the mechanism of Prozac and other ssri's:

viewtopic.php?f=68&t=1964

Thanks! Though I find the linked evidence to be clearly insufficient to explain the SSRI issue.

Most SSRI's raise levels of allopregnanolone, which has undisputed antidepressant and neurogenesis effects. You can search Google for "Prozac allopregnanolone". However, it only happens after 2-4 weeks, which may explain why people are much more likely to commit suicide in the first 2 weeks of SSRI use when the only thing they do is raise serotonin. I posted a study recently where even big pharma said the theory is wrong and backwards - i.e. serotonin causes depression. In addition, fluoxetine (Prozac) is a 5-HT2 receptor antagonist, similar to mianserin and cyproheptadine btoh if which are known to be antidepressants. So, at least some of the SSRIs seem to be a mixed bag in terms of serotonin and also have desirable side effects on neurosteroids.

Thanks haidut!!! Very interesting info as always. I didn't know about the existence of allopreg. Apparently it's synthesized after progesterone, not pregnanolone itself.

I am interested in your views on why there's a mass of evidence in pubmed studies, clinical practice and anecdotal stories of direct serotonin precusors to alleviate or heal (while under treatment) depression and anxiety. I mean 5-HTP and L-Tryptophan.

I never found an explanation for that on RP's articles.

I just responded to you question as part of another post in the same thread. Tryptophan per se is not very bad but most of its metabolites are very very dangerous and serotonin is just one example. So, Peat may be just being practical and avoiding the whole cascade by simply avoiding tryptophan.
The studies on using free amino acids for cancer show that as little as 500mg tryptophan daily combined with the proper ratio of other essential amino acids is enough to put you in an anabolic state without being pro-carcinogenic as a result of its metabolites. However, we get a lot more than 500mg of tryptophan from our protein and the more we age the more likely we are to metabolize it into one of the toxic byproducts. So, the positive effects of glycine and BCAA are probably due to the inhibition of toxic tryptophan metabolism as well as boosting the thyroid, which tryptophan itself may inhibit.

 

[haidut]

I observed my son go into depression from adding whey protein, melatonin, and then 5htp in approximately 2 weeks. The 5htp was the straw that broke the camel's back. It killed his appetite which lowered his metabolism. He first stopped leaving the house and then his bedroom. He became light and then noise sensitive. His appetite diminished. He became angry and severely depressed. I have never seen him this depressed. It was awful and frustrating since information online says that it helps anxiety and depression.

Yes, tryptophan in compromised people can and usually is very dangerous. But the solution is probably not avoiding it completely but ensuring it stays in the body as tryptophan and as close to the minimum required essential quantity as possible. I am not sure that completely devoid of tryptophan we can maintain proper muscle mass or even survive. For instance, tryptophan seems to be anabolic for muscle and liver and the positive effects from BCAA and glycine seem to be from reduction of toxic trytophan metabolites like serotonin and in effect increasing tryptophan bioavalability.
http://www.ncbi.nlm.nih.gov/pubmed/3357059
http://www.ncbi.nlm.nih.gov/pubmed/1722997

From the first study above:
"...The effect of dietary tryptophan on ribosomal protein synthetic activity in porcine muscle, however, is similar to the observations of Sidransky, Murty and Verney (7) who reported correlations in rat liver in ribosomal activity with total protein synthesis. This indicates that the findings of Sidransky, Murty and Verney that tryptophan has a hormone-like ability to promote protein synthesis may apply to tissues other than the rat liver."

Btw, caffeine does something very similar - it increases tryptophan and decreases serotonin in the brain.
http://www.ncbi.nlm.nih.gov/pubmed/6207403
http://www.ncbi.nlm.nih.gov/pubmed/25738401
http://www.ncbi.nlm.nih.gov/pubmed/20507554
http://www.ncbi.nlm.nih.gov/pubmed/11445277
http://www.ncbi.nlm.nih.gov/pubmed/8039038

 

[HDD]

I observed my son go into depression from adding whey protein, melatonin, and then 5htp in approximately 2 weeks. The 5htp was the straw that broke the camel's back. It killed his appetite which lowered his metabolism. He first stopped leaving the house and then his bedroom. He became light and then noise sensitive. His appetite diminished. He became angry and severely depressed. I have never seen him this depressed. It was awful and frustrating since information online says that it helps anxiety and depression.

Yes, tryptophan in compromised people can and usually is very dangerous. But the solution is probably not avoiding it completely but ensuring it stays in the body as tryptophan and as close to the minimum required essential quantity as possible. I am not sure that completely devoid of tryptophan we can maintain proper muscle mass or even survive. For instance, tryptophan seems to be anabolic for muscle and liver and the positive effects from BCAA and glycine seem to be from reduction of toxic trytophan metabolites like serotonin and in effect increasing tryptophan bioavalability.
http://www.ncbi.nlm.nih.gov/pubmed/3357059
http://www.ncbi.nlm.nih.gov/pubmed/1722997

Btw, caffeine does something very similar - it increases tryptophan and decreases serotonin in the brain.
http://www.ncbi.nlm.nih.gov/pubmed/6207403
http://www.ncbi.nlm.nih.gov/pubmed/25738401
http://www.ncbi.nlm.nih.gov/pubmed/20507554
http://www.ncbi.nlm.nih.gov/pubmed/11445277
http://www.ncbi.nlm.nih.gov/pubmed/8039038

He was definitely compromised from a recent overdose/withdrawal from phenibut.

He switched to a rice bran protein powder that has less tryptophan and stopped taking 5htp and is doing much better now.

 

[TheHound]

has anybody else experienced the balance problems listed? Im going to be doing something over the weekend that requires some moderate balancing and I was just wondering if I should wait until after to start taking l-lysine

 

[GAF]

I have been taking 500x3 per day lysine for about a month. I partner dance several nites a week. I whirl. I Twirl. I spin and I stop on a dime. The Lysine has not caused a single balance problem for me. If it did, I would know it immediately. Serotonin must die!

 

[jyb]

Egg whites are claimed to be 60% anabolic and are a rich source of cystein and glycine, which combined raise glutathione lilke no other natural substance.

I always find odd the fact that egg protein are considered the ultimate useful source of protein and not milk. I would have thought that milk should be the most physiological source since it fuels growth of *humans* since birth. (Unless human milk is more anabolic than cow milk and eggs?!) Clearly milk is extremely anabolic at birth at least - babies don't need to supplement protein to grow like they do.

 

[haidut]

Egg whites are claimed to be 60% anabolic and are a rich source of cystein and glycine, which combined raise glutathione lilke no other natural substance.

I always find odd the fact that egg protein are considered the ultimate useful source of protein and not milk. I would have thought that milk should be the most physiological source since it fuels growth of *humans* since birth. (Unless human milk is more anabolic than cow milk and eggs?!) Clearly milk is extremely anabolic at birth at least - babies don't need to supplement protein to grow like they do.

Yeah, I find it odd too but the studies I have seen so far all claim the same thing. Maybe the egg industry got involved somehow and flooded the science with pro-egg studies.

 

[Makrosky]

Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.

And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.

Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.

One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...

This thread has a study shedding light on the mechanism of Prozac and other ssri's:

viewtopic.php?f=68&t=1964

Thanks! Though I find the linked evidence to be clearly insufficient to explain the SSRI issue.

Most SSRI's raise levels of allopregnanolone, which has undisputed antidepressant and neurogenesis effects. You can search Google for "Prozac allopregnanolone". However, it only happens after 2-4 weeks, which may explain why people are much more likely to commit suicide in the first 2 weeks of SSRI use when the only thing they do is raise serotonin. I posted a study recently where even big pharma said the theory is wrong and backwards - i.e. serotonin causes depression. In addition, fluoxetine (Prozac) is a 5-HT2 receptor antagonist, similar to mianserin and cyproheptadine btoh if which are known to be antidepressants. So, at least some of the SSRIs seem to be a mixed bag in terms of serotonin and also have desirable side effects on neurosteroids.

Thanks haidut!!! Very interesting info as always. I didn't know about the existence of allopreg. Apparently it's synthesized after progesterone, not pregnanolone itself.

I am interested in your views on why there's a mass of evidence in pubmed studies, clinical practice and anecdotal stories of direct serotonin precusors to alleviate or heal (while under treatment) depression and anxiety. I mean 5-HTP and L-Tryptophan.

I never found an explanation for that on RP's articles.

I just responded to you question as part of another post in the same thread. Tryptophan per se is not very bad but most of its metabolites are very very dangerous and serotonin is just one example. So, Peat may be just being practical and avoiding the whole cascade by simply avoiding tryptophan.
The studies on using free amino acids for cancer show that as little as 500mg tryptophan daily combined with the proper ratio of other essential amino acids is enough to put you in an anabolic state without being pro-carcinogenic as a result of its metabolites. However, we get a lot more than 500mg of tryptophan from our protein and the more we age the more likely we are to metabolize it into one of the toxic byproducts. So, the positive effects of glycine and BCAA are probably due to the inhibition of toxic tryptophan metabolism as well as boosting the thyroid, which tryptophan itself may inhibit.

haidut, sorry for the delay answering. Thanks a lot for the sound info man! i didn't know all that and the cancer stuff. That is a beginning of a possible explanation. It makes more sense that just what Ray says. Anyway, why are only the tryptophan metabolites the only dangerous ? Strange than nature put such dangerous metabolites in just one essential aminoacid and left the others "clean". Strange.

-----

For the Prozac issue: Then drugs like SSRI should be considered not only safe but beneficial after the first 2-3 weeks of serotonin raising ?

Cheers