Serotonergic modulation of glutamate neurotransmission

This is for hypothesis and even educated speculation.
Blueturtle
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Re: Serotonergic modulation of glutamate neurotransmission

Unread post by Blueturtle »

Mesolimbo wrote:
Blueturtle wrote:Researchers looking at the paper results in 3 studies discussing persistently impaired sexual behaviour from neonatal citalopram, 5-ht1b agonist, and clomipramine suggested that the data looks like these persistent negative effects on sexuality in these early treated animals is likely the result of abnormal stimulation of the 5-HT1b and 5-ht2a receptors.
I think 5HT1B/D receptors downregulation plays a significant role in causing some of our symptoms. It's going to be difficult to upregulate these receptors again with the abnormally elevated serotonin level. I think a partial agonist is the only option.

Sumatriptan (5HT1B/1D full agonist) gave me one of the first "windows" with amelioration of many of the symptoms, but the effect was short-lived as rapid tolerance set in. This shouldn't happen with a partial agonist.

WAY-100135, a research compound, is a 5HT1B/1D partial agonist and 5HT1A antagonist. It looks very interesting, at least on paper.

Given that SERT is downregulated semi-permanently, a partial agonist of 5HT1 receptor (all subtypes) with moderate to high intrinsic activity would be beneficial, I reckon, for limiting serotonin transmission somewhat and offering some symptomatic relief without causing tolerance.
It helps solidify some of the animal data with the fact that the medication helped you. That med is a migraine medication, I read somewhere that people who suffer from migraine headaches often have very high sex drives.
PSSD from citalopram.
Took it Winter 2012-Summer 2016
Cut cold turkey. Symptoms include genital anesthesia, ejaculatory anhedonia, low libido, Burning/tingling genital pain.
My story: http://www.pssdforum.com/viewtopic.php?f=14&t=2536
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Re: Serotonergic modulation of glutamate neurotransmission

Unread post by continue »

Mesolimbo = Area1255 ?

those ideas + treatments options are very similar
Jaxx
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Re: Serotonergic modulation of glutamate neurotransmission

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continue wrote:Mesolimbo = Area1255 ?

those ideas + treatments options are very similar
no
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JayR
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Re: Serotonergic modulation of glutamate neurotransmission

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continue wrote:Mesolimbo = Area1255 ?

those ideas + treatments options are very similar
Haha, nice try. But I am Area1255! :lol:
Half-alive
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Re: Serotonergic modulation of glutamate neurotransmission

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No, I am Area1255!
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Snake
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Re: Serotonergic modulation of glutamate neurotransmission

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Stop fooling around, I'm Area1255.
Finding a cure is only a matter of time! Never quit!
Trazedy
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Re: Serotonergic modulation of glutamate neurotransmission

Unread post by Trazedy »

I write my story because I believe it to be very representative of the cortisol-glutamate theory.

I've always been over anxious and emotional. I also cry extreamely easely. I was also hypersexual meaning easely aroused and high libido, even if usually I had sex/masturbation 3-4 a week, max once a day.

On 2013 I started having insomnia

On 2014 I took 6 months of Paroxetine 20mg aimed at curing a bowel syndrom (SIBO) with no result nor side effects.

On January 2018 I started having bad insomnia after a surgery due to health worries. I also started working as a pizza chef staying up late and having a lot of stress working in a crazy environment untill 22pm.

On June 2018 I took Prednison 25mg for 20 days aimed at curing an inflammation. It did not work but it made me maniac, I was sleeping 2h at night, having constant headache anxiety. The day I quit it I got some sort of withdrowal with extreme cold, shaking and axiety attacks. I also started waking up for no reason at 7am (instead of the usual 12-13am), not having enough rest, this while working on the same night job that was getting more and more difficult because on summer people eat way more pizzas.

The insomnia did not resolve at all, I was always tired and waking up at 7am (cortisol rebound?).

On August 2018 my girfriend left me after almost 5ys and I went nuts. Since I needed to sleep I went to a psychiatrist who gave me venlaflaxine 75mg, I took it for 9 days but it was difficult for me to get erections. I also took some pill of SAM-e and some night I took lorazepam. Having sexual problems I learnt about PSSD and I was extremely scared, so I called the shrink advised me to take Trazodone instead. I quit lorazepam, venlaflaxine and SAM-e at the same time.

Sexual functioning came back the next day and on my first dose of Trazodone (75mg) I had some sort of psychedelic experience while sleeping (caused by the trazodone metabolite mCPP ?). I slept 13h insted of the usual 4. Then the 2nd day it stopped working and after a week I called the shrink asking for a higher dose but she told me to stick to 75mg. So for 2 weeks I took Trazodone and I kept working, sleeping 4h, waking up at 7am precisely and having a lot of anxiety thinking about my ending relationship. After 14 days I started noticing penish shrinkage and poor genital blood flow. I thought it was stress and nocebo effect. After 28 days I realized it was not psychological, I had a baby penis extremely white with no blood flow so I got extremely scared, like panic attacs and crying because I realized I was experiencing PSSD and I quit cold turkey. I had a terrible withrawal and at the same time I got a nightmarish viral flu. I was somehow able not to kill myself because the withrawal made me maniac. After a month penish shrinkage disappeared but PSSD with no libido, ed and genital anesthesia remained. Strangely for the first months I also had bellybutton anesthesia.

I also had slightely high prolactin that lowered after some months.

Insomnia and 7am waking only got better on May 2019.

I tried melatonin for some day and it gave me STRONG morning erections and better libido but I thought it was better not to mess with my brain whithout a plan.

Since melatonin COMPLETELY reverses my insomnia, tiredness and morning wakings, I though it
was a cortisol problem so tested morning cortisol, morning acth and urine 24h cortisol and they were all ok. Prolactin and free/total testosterone are fine.

But I tested cortisol after almost a year from my peak insomnia and my morning waking were already gone.

On may 2019 one evening I switched from 0 sensitivity and 0 orgasm to 40% of both. Two hours later I got 38°C fever. Improvement was immediate and lasted after the fever.

On the end of the same month in order to try tu cure the same old inflammation, I did 2 injections/day of 1mg ceftriaxone for 4 days. So 2mg at day, 8mg in total. After not even 48h since the first injections I exterienced an extreme worsening of ed, shrinking, and sexual dysfunction in general. No change in sensitivity but a big change in ejaculation. I started drippong sperm with no contraction or strenght. Orgasm also worsened.

I realized cetfriaxone is a potent GLT1 and xCT upregulating drug, at my dose we are talking about a possible increase up to treefold, so my glutamate level drastically dropped. It also has long lasting effects, we are talking about AT LEAST 2 months, possibly permanent.

https://www.nature.com/articles/nature03180

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918547/

http://europepmc.org/articles/pmc3741415

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988910/



On June 2019 I got a bad gastroenteritis because ceftriaxone also ruined my bowel, so I got fever again, 39°C and I got a new improvement in skin sensitivity, like from previous 40% to 60-70%. The effect is lasting. Shrinkening went away but I stil have post ceftriaxone ejaculation problems.

1 or 2 days after the end of the fever, I got a bad allergy with sneezing (It almost never happens to me). The next morring I woke up with full erection and 90% recovery in all aspects except ejaculation. Libido was 100% back. It lasted not even 48h. (histamine?)

Now I have senstivity and orgasm improvement due to fever and ejaculation and orgasm worsening due to ceftriaxone. So orgasm is better and worse at the same time, mentally better but phisiologically worse. You need phisical contractions for mental orgasm otherwise it feels like a ruined orgasm that FemDom people practice.

This whole story means that glutamate is extremely involved in erection, shrinking and orgasm. Skin sensation and orgasm can improve immediately and long lasting after fever, they might also be related to the same receptor. Probably high dose Prednisone and SAM-e have a big role in my PSSD.

I don't know what is my situation with 5ht2 since trazodone is a potent antagonist but its metabolite mCPP is a potent agonist. I know for sure that melatonin for me helps A LOT on erections and enough on libido.

I don't also know if my trazodone PSSD is different from regular SSRI PSSD.

My symptoms now
PSSD: ed, no libido, no spontaneus erections, no morning erections, weak skin sensation and orgasm. Possibly a right testicle shrinking.

Post Ceftriaxone Sexual Dysfunction: ejaculation and sperm consistency worsened and they make me not enjoy my orgasm recovery.

Any thought/solution? I cannot digest garlic, I tolerate proteins but not carbs/sugars. Low libido/lack of spontaneus erections bother me the most but I also need to fix ceftriaxone mess.
Neuroscience MD researcher. Ita Male 30yo.

28 pills of Trazodone 75mg on Sept '18. Cold Turkey.
1y severe penis shrink/numb/ED
4y ED 7/10+numb 5/10+orgasm 3/10+libido 0
5y ED 9/10+numb 8/10+orgasm 6/10+libido 2
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Meso
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Re: Serotonergic modulation of glutamate neurotransmission

Unread post by Meso »

Trazedy wrote: My symptoms now
PSSD: ed, no libido, no spontaneus erections, no morning erections, weak skin sensation and orgasm. Possibly a right testicle shrinking.

Post Ceftriaxone Sexual Dysfunction: ejaculation and sperm consistency worsened and they make me not enjoy my orgasm recovery.

Any thought/solution? I cannot digest garlic, I tolerate proteins but not carbs/sugars. Low libido/lack of spontaneus erections bother me the most but I also need to fix ceftriaxone mess.
Thanks for sharing your story. As of now, to temporarily restore glutamatergic functioning and reverse some of PSSD, people are having success with shrooms (Psilocybin), but unfortunately the effects aren't long-lasting. Alcohol hangover also works for some people, but that also isn't long-lasting. I tried Prednisolone for a while and it made me horny but also gained weight over-rapidly on it, so I had to quit taking it.

Other than downregulating GR, I don't know how to restore glutamatergic signalling permanently. The problem with downregulating GR though is that too much HPA reactivity would mean too much cortisol again, causing hippocampal shrinkage = depression and anxiety.
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