Serotonin Dominance And How To Deal

[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, 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

Well, to be fair it should be said that cysteine, methionine, arginine and asparigine all have dangerous metabolites that can impact conditions such as cancer. Of these, arginine is probably the most nefarious due to its conversion of NO, which is a universal metabolic poison for every cell.
Why most of the tryptophan metabolites tend to be toxic I don't know. Since it exists in virtually all protein except gelatin it could be a mechanism for controlling how much protein we eat. It could also be a situation similar to iron - we need a lot while young but at older age it's better to be copper dominant. Ray said that our tryptophan requirements decrease greatly with age but he did not elaborate why. The same seems to be true with cysteine, methionine and arginine. There are studies with all of these aminos showing reduced intake improved health and/or increased lifespan.

 

[lexis]

A clue may come from a previous study that showed the drug poisons yeast that can’t make the amino acid tryptophan, which cells need to manufacture proteins. Polymenis and colleagues found that tryptophan levels declined in yeast cells exposed to ibuprofen. They also showed that the drug spurs destruction of a protein that enables cells to absorb tryptophan.

http://news.sciencemag.org/biology/2014 ... life-spans

 

[haidut]

A clue may come from a previous study that showed the drug poisons yeast that can’t make the amino acid tryptophan, which cells need to manufacture proteins. Polymenis and colleagues found that tryptophan levels declined in yeast cells exposed to ibuprofen. They also showed that the drug spurs destruction of a protein that enables cells to absorb tryptophan.

http://news.sciencemag.org/biology/2014 ... life-spans

Thanks. Incidentally, high dose (3g - 6g) aspirin also seems to deplete tryptophan, so this may explain why aspirin has also been shown to extend lifespan.
http://jmm.sgmjournals.org/content/52/5/409.long

"...We also found that aspirin at high doses (1 and 2 mM) inhibited the formation of chlamydial inclusion bodies and proliferation of the bacterium within inclusion bodies in HEp-2 cells. These results suggest that the anti-chlamydial activity of aspirin might be associated with the inhibition of host-cell metabolism, including depletion of essential factors during chlamydial growth. Support for this assumption comes from the finding that the inhibition of chlamydial growth by aspirin was overcome when tryptophan was added to the culture medium."

 

[bruschi11]

@natedawggh I threw this thread out there yesterday.

How Excess Cortisol/serotonin Inhibits Or Lowers Dopamine?

Very interested to hear about where you are at with this serotonin dominance issue you've had. I actually moved to Ritanserin (1mg with breakfast) today from Cypro and will end up trying Metergoline as well.

Will say I am actually allergic to aspirin so cannot use that. I have begun PEATING and I have a pro-dopamine supplement protocol I have began. Tyrosine, taurine, theanine, creatine, vitamins a, c, d. I am currently on TRT with and hcg along with use of androsterone/5adhp/dhea (5mg each daily).

While I am now currently blocking serotonin at the receptors. Systemic depletion of serotonin seems like what I will need to do.

@haidut would love to hear your thoughts here as well. I am very lucky I found this site and my internet "googling" allowed me to figure out what was going on. I can tell you this- it was a very long scary month until I finally got Cypro in my system. I'm not well right now, but I am sure now that I will get ahold of this.

I have a bunch of lab work coming back- (saliva cortisol, hormonal bloodwork, 24 hour urine test, and will be having a neurotransmitter test later this week.) I moved back into my parents house for the time being as I know I have a long road ahead of me back to optimum health.

Lastly, over all of my blood tests over the last 4 years, vitamin B12 has always been significantly above range. I emailed Ray and he said that the B12 could signify SIBO (small intestine bacteria overgrowth) that led to all my problems. Hence- my beginning to PEAT just this week.

 

[haidut]

@natedawggh I threw this thread out there yesterday.

How Excess Cortisol/serotonin Inhibits Or Lowers Dopamine?

Very interested to hear about where you are at with this serotonin dominance issue you've had. I actually moved to Ritanserin (1mg with breakfast) today from Cypro and will end up trying Metergoline as well.

Will say I am actually allergic to aspirin so cannot use that. I have begun PEATING and I have a pro-dopamine supplement protocol I have began. Tyrosine, taurine, theanine, creatine, vitamins a, c, d. I am currently on TRT with and hcg along with use of androsterone/5adhp/dhea (5mg each daily).

While I am now currently blocking serotonin at the receptors. Systemic depletion of serotonin seems like what I will need to do.

@haidut would love to hear your thoughts here as well. I am very lucky I found this site and my internet "googling" allowed me to figure out what was going on. I can tell you this- it was a very long scary month until I finally got Cypro in my system. I'm not well right now, but I am sure now that I will get ahold of this.

I have a bunch of lab work coming back- (saliva cortisol, hormonal bloodwork, 24 hour urine test, and will be having a neurotransmitter test later this week.) I moved back into my parents house for the time being as I know I have a long road ahead of me back to optimum health.

Lastly, over all of my blood tests over the last 4 years, vitamin B12 has always been significantly above range. I emailed Ray and he said that the B12 could signify SIBO (small intestine bacteria overgrowth) that led to all my problems. Hence- my beginning to PEAT just this week.

Let me know when you get the lab results. Serotonin is the primary driver of systemic cortisol synthesis due to raising both CRH and ACTH. Cyproheptadine should lower cortisol, but thyroid should be boosted as well since rising serotonin is usually a symptom of low thyroid function.

 

[bruschi11]

My original bloodwork on 12/20/2016 showed cortisol at 23, range (10-19). This was also at 11am when it was supposed to be at 8am. My testosterone was very low (250 range) most likely due to all the excess cortisol sucking T cream in rapidly. I immediately tripled testosterone dosage upon seeing these results. May move to Cypionate soon.

In the past, when I have had low-end saliva cortisol, I have seen blood cortisol between 13 and 16 in morning. When I had saliva cortisol on the top of the range, my blood cortisol was at 19. So it's painfully obvious when I get this saliva cortisol back we'll see this being very high probably all day (symptoms actually got worse as day went on).

I should be getting saliva cortisol back today, tomorrow the latest I'd say unless my doctor/the lab is being very lazy not following protocol.

I have begun to take my normal t3 dose again (5mcg 4 times a day) within last 3 days. Originally was doing this for 7 months straight. I believe stopping it on December 8th- I believe this possibly more than FINASTERIDE caused my issues. Stopped FIN on November 15th. Definitely wasn't the same afterward, but it took until the t3 miscue to really start causing my issues and lack of sleep/anxiety/inability to handle stress.

 

[haidut]

My original bloodwork on 12/20/2016 showed cortisol at 23, range (10-19). This was also at 11am when it was supposed to be at 8am. My testosterone was very low (250 range) most likely due to all the excess cortisol sucking T cream in rapidly. I immediately tripled testosterone dosage upon seeing these results. May move to Cypionate soon.

In the past, when I have had low-end saliva cortisol, I have seen blood cortisol between 13 and 16 in morning. When I had saliva cortisol on the top of the range, my blood cortisol was at 19. So it's painfully obvious when I get this saliva cortisol back we'll see this being very high probably all day (symptoms actually got worse as day went on).

I should be getting saliva cortisol back today, tomorrow the latest I'd say unless my doctor/the lab is being very lazy not following protocol.

I have begun to take my normal t3 dose again (5mcg 4 times a day) within last 3 days. Originally was doing this for 7 months straight. I believe stopping it on December 8th- I believe this possibly more than FINASTERIDE caused my issues. Stopped FIN on November 15th. Definitely wasn't the same afterward, but it took until the t3 miscue to really start causing my issues and lack of sleep/anxiety/inability to handle stress.

Ray wrote via email to a lady asking about her husband with similar symptoms and lab results that hypothyroidism in males is characterized by increased cortisol/prolactin and decreased T and DHEA levels. He recommended pregnenolone, thyroid, aspirin, and small dose DHEA. All of these happen to lower/oppose cortisol and raise gonadal synthesis of androgens.

 

[bruschi11]

Aspirin I am allergic too- deathly allergic actually. This is going to be a lot more than just the naturals as I have been doing above. High dose Preg was involved for 7 months before this all happened- systemic preg levels were in the 300 range (very high). I think PREG is great, but cholesterol--> Preg is so fast right now I don't think I need it.

I actually have PROG that I will be starting shortly to replace PREG.

Drug intervention was 100% needed with Cypro and now Ritanserin. I am thinking that based on the fact that you wrote of Serotonin inhibition does not occur with these antagonists, I may start using Lisuride once a week or so to get the Dopamine receptors going a bit while actually inhibiting serotonin creation.

This all really depends on my neurotransmitter test though. I really need to see systemic levels of both serotonin and dopamine to realize whether this is a systemic issue or a receptor issue. I'd think its definitely a systemic issue for serotonin, but we can't say yet for dopamine.

 

[Aflac]

@bruschi11
How did the cypro, ritanserin, and Lisuride work out? Did you end up trying all of these? Am thinking of trying these

 

[bruschi11]

@Aflac decently but killed libido. I was already low in histamine so I think these being antihistamines killing me.

 

[Aflac]

I wonder if the cypro or ritanserin could help sleep through the night consistently. I string together a few good nights of sleep and I feel more normal. But it's only ever 2 or 3 nights. Then my sleep is ***t for a night or 2. If I could just get a week or two with no bad nights of sleep at all that would be huge. Is this type of sleep a problem for you still, did these help in that regard?

Wondered about the lisuride for improving orgasm but not ready to risk a dopamine withdrawl, sounds horrible. Can't be much worse than pfs, but my god I would not be surprised