I am going to drop a major bomb soon

This is for hypothesis and even educated speculation.
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guacamo
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I am going to drop a major bomb soon

Unread post by guacamo »

First of all i want you to get familiar if you already are not with the PSSD cured cases in regard to serotonin and 5-HT1A receptor:
St John Wort cured cases:
https://pssdlab.wordpress.com/kramdrol-st-johns-wort/
https://pssdlab.wordpress.com/beetlebum-st-johns-wort/
https://www.reddit.com/r/PSSD/comments/ ... cure_pssd/
SJW -serotonin reuptake inhibition without affecting SERT, 5-HT1A agonist

Inositol cured cases:
https://pssdlab.wordpress.com/pssd-inositol/
https://pssdlab.wordpress.com/pharmd-inositol/
https://www.reddit.com/r/PSSD/comments/ ... _inositol/
Inositol - second messenger for serotonin

Other cured cases i want you to become familiar with:

https://www.pssdforum.org/viewtopic.php?f=10&t=2560 Mushrooms+MDMA
mechanism of action of mushrooms on 5-HT1A: 5-HT1A agonist, mechanism of action of MDMA: 5-HT1A agonist and serotonin reuptake invertion (SERT instead of reuptaking serotonin is pumping serotonin outside of synapse)

https://www.reddit.com/r/PSSD/comments/ ... _tramadol/
Mushroom on 5-HT1A: agonist, Tramadol - SNRI

https://pssdlab.wordpress.com/pete-low-dose-ssri/
mechanism of action - SSRI
fred1234 wrote: Tue Sep 05, 2017 5:30 am I wanted to post a little update after my trial with Venlafaxine. I upped the dose till half of 37,5. It made me very horny at the beginning but then the effect started to fade away. I stopped it without many problems and now it seems like pssd is not a problem anymore. I live in a nice relationship with a very satisfying sexuality. I wake up with morning erections every morning, have sexual thoughts, kind of everything is almost as it was before I started sertraline when I was 25. Now I am 33 so a little bit less lust might be normal due to the age. So for me the experiment was a success. Good luck to you!
mechanism of action - SNRI
Bunny wrote: Thu Aug 16, 2018 5:43 pm The last time people heard from me - in this thread - I was experimenting with Addyi and getting treatment for my PTSD. It turns out that Addyi did not do anything for me, and I discontinued after three months. Sometime in May, my psychiatrist prescribed lithium for my depression because I told him I was tired of SSRIs and their horrible side effects. I worked up to 450mg of lithium and have remained there. Combined with intensive psychotherapy and twelve weeks of pelvic floor therapy, I can now say that I am completely cured. I experience sexual desire, fantasies, lubrication, it's all back. It's like being back to my pre-SSRI self. These effects have remained since June or so. (For my OCD, I am actually low-dosing paroxetine, but this hasn't had an effect on my sex drive at all.)

After ten years, the nightmare is finally over. I want to kick myself because the solution was there in plain sight the whole time. This is why it is so important to be heard by your healthcare providers -- I was written off for years by psychiatrists, gynecologists, and even myself; I had too much pride to face my repressed emotions and deep, deep, deep psychological issues. I was very fortunate to find providers who would listen to me and not automatically prescribe SSRIs or tell me that sexual functioning is "not important for women." Ironically, when I decided that I was going to get my mental health in order before I considered my sexual functioning, that is when sexual functioning returned.

The future looks bright now. I still have OCD, but I'm finding a way to work through it. My many thanks to the people on this forum who remained positive and recommended treatments. I hope that everyone can find the same relief I have.

I'll be making one last post in my introductory thread, and then I will probably only check back here once in a while.
Lithium increases serotonin in the brain and sensitizes post-synaptic 5-HT1A receptors
elkikko wrote: Sat Apr 11, 2015 11:30 am I found a man on Facebook that has serious PSSD. He has solved with Valproic acid, bupropion, Nebivolol max 5mg/day, moclobemide. Thats the cure, good luck. Actually im trying buspar
Moclobemide - monoamine oxidase A (the one that degrades serotonin)
Bear wrote: Tue Jul 24, 2018 3:02 am Some very good news

A man in the PSSD Facebook group has fully recovered after microdosing with ibogaine capsules during nine days of treatment. Five doses were taken every second day after the first dose - the first three doses were 200mg each (3.7mg/kg body weight), the fourth dose was 320mg (5.9mg/kg) and the fifth dose was 350mg (6.5mg/kg). This treatment was administered at [redacted clinic name]

Our friend reported feeling fully recovered after the very first dose, taken on the 4th of July. Last I spoke to him was on the 22nd, and he claims that he still feels 100% recovered from all aspects of the condition. While this may raise some suspicions, Dylan was a very active member of the group and was clearly deeply affected by emotional and sexual issues, reporting all the hallmark symptoms of PSSD - including severe emotional blunting, genital anaesthesia and low libido. He often expressed suicidal feelings and generally wrote in a very negative tone. While I too regard every recovery story with scepticism at first, I have difficulty seeing untruthfulness in any part of his story. Visiting his profile, I could even see a family member of his wishing him 'recovery' of some sort.

I am hopeful that ibogaine could prove to be a beneficial substance to other sufferers. It is, however, very expensive - especially under clinical supervision. There is also an issue with legality as it is classified as a Schedule I drug throughout the US. However, in Australia, Canada and New Zealand it is accessible through experimental treatment facilities via prescription and in the UK it is unscheduled. Having shown great promise in treating other drug-induced problems, I think that this is highly worth looking into.

PSSD Facebook group: https://www.facebook.com/groups/1813492682283042/

Some of the information here comes from a conversation I had with him through instant messaging. Message me or join the Facebook group and reach out to the OP (just search 'ibogaine') if you need anything clarified.
Ibogaine - SSRI
siebs1122 wrote: Fri Jul 07, 2017 3:02 am Hey guys, just wanted to give another update. Since taking low dose metergoline from January-Feburary as well as forskolin, then stopping, I have had long-lasting improvements in every aspect of my PSSD.

I noticed that I never really had a proper introduction on this forum explaining my history and symptoms, so I will take this opportunity to give a brief background.

I started SSRIs back in the beginning of 2014 for OCD, when I was 17 years old. I had no history or symptoms of depression or any other mental illness, aside from OCD when I began SSRIs. Even with the OCD, I was always happy and optimistic and if anything, was over-emotional. I initially tried Luvox and Paxil, both which made my OCD worse and caused a lot of side effects, including sexual dysfunction. However, upon discontinuation of both of these medications, my sexual functioning returned to normal and the side effects went away. It wasn't until my third SSRI, lexapro, that I acquired PSSD. I was on this medication for about 2 months then discontinued because it was making my OCD 100x worse as well as causing many side effects, just like Luvox and Paxil did. However, upon discontinuation, my sexual functioning did not return to normal (weak erections, anorgasmia, genital numbness) and I had many other lexapro-induced side effects that persisted long after discontinuation too(dry mouth, increased appetite, insomnia, photosensitivity, emotional anhedonia, general anxiety, worsened OCD, etc.) I lived like this for 3 years until coming across this forum and soon began experimenting with supplements. I tried inositol, magnesium, and NAC- all to no avail. I then tried circumin, which worsened my PSSD. I was beginning to lose hope until I tried forskolin. I didn't feel an effect from it until about 1 week after starting it, when I noticed a tingling sensation in the back of my head one night. It was a distinct tingling sensation that went from the back of my head, down my spine. The next mourning, I noticed I awoke with a strong erection and my anxiety and other symptoms were significantly better. This electrical sensation in the back of my head came and went, and my PSSD increasingly improved. I soon added metergoline to the forskolin and micro dosed on it for the next month. Over the course of that month, my PSSD and related symptoms virtually disappeared. My sexual functioning is close to pre-SSRI levels and my emotional capacity is well over 80% back. The other side effects that I had from lexapro, like dry mouth and general anxiety are now all gone as well. I feel pretty much how I used to pre-lexapro, albeit certain aspects like motivation are still low.

Although I know many people on here have experimented with forksolin and metergoline, I think more people should, especially the ones who have PSSD from lexapro (which is quite a few). I am sorry for the long post but I hope my partial-success story from metergoline shows that their is hope for this condition and it's not permanent. I am a firm believer that the problem purely lies in simply finding a way to efficiently antagonize 5h2a/2c and up regulate dopamine receptors.
Metergoline - 5-HT1A agonist


Now i want to present you my thesis: 5-HT1A receptor is involved in PSSD in a way that when people are cured this receptor is agonized, not antagonized. Why desensitized receptor is not responding to antagonists, but to agonists? First of all what is needed to be known is that not everything in the brain works in a negative feedback manner (like taking agonists always decreases receptor expression and agonist always increases), to name a few 5-HT2A, D2, post-synaptic 5-HT1A.
In these cases either there was more serotonin, thus 5-HT1A was more activated via that, or 5-HT1A agonism, sometimes very strong like in mushrooms+MDMA case.
Now we need to answer another question - what is pre-synaptic and post-synaptic involvement in PSSD with help comes to us this paper: https://www.frontiersin.org/articles/10 ... 00040/full
some of the interesting parts:
Brain serotonin (5-HT) neurotransmission plays an important role in male sexual behavior and it is well established that activating 5-HT1A receptors in rats facilitate ejaculatory behavior. However, the relative contribution of 5-HT1A somatodendritic autoreceptors and heteroreceptors in this pro-sexual behavior is unclear. Moreover, it is unclear whether the contribution of somatodendritic 5-HT1A autoreceptors and postsynaptic 5-HT1A heteroreceptors alter when extracellular 5-HT levels are chronically increased. . Serotonin transporter knockout (SERT–/–) rats exhibit enhanced extracellular 5-HT levels and desensitized 5-HT1A receptors. These rats model neurochemical changes underlying chronic SSRI-induced sexual dysfunction. We want to determine the role of presynaptic versus postsynaptic 5-HT1A receptors in the pro-sexual effects of 5-HT1A receptor agonists in SERT+/+ and in SERT–/– rats. Therefore, acute effects of the biased 5-HT1A receptor agonists F-13714, a preferential 5-HT1A autoreceptor agonist, or F-15599, a preferential 5-HT1A heteroreceptor agonist, and S15535 a mixed 5-HT1A autoreceptor agonist/heteroreceptor antagonist, on male sexual behavior were assessed. A clear and stable genotype effect was found after training where SERT+/+ performed sexual behavior at a higher level than SERT–/– rats. Both F-15599 and F-13714 induced pro-sexual activity in SERT+/+ and SERT–/– animals. Compared to SERT+/+, the F13714-dose-response curve in SERT–/– rats was shifted to the right. SERT+/+ and SERT–/– rats responded similar to F15599. Within both SERT+/+ and SERT–/– rats the potency of F-13714 was much stronger compared to F-15599. S15535 had no effect on sexual behavior in either genotype. In SERT+/+ and SERT–/– rats that were selected on comparable low sexual activity (SERT+/+ 3 or less ejaculations and SERT–/– 5 or less ejaculations in 10 weeks) S15535 also did not influence sexual behavior. The two biased compounds with differential effects on 5-HT1A auto- and hetero-receptors, exerted pro-sexual activity in both SERT+/+ and SERT–/– rats.
F-15599 is a preferential heteroreceptor agonist, but at higher doses used in this study it actually becomes highly selective 5-HT1A autoreceptor agonist (F15599 is post-synaptic and pre-synaptic receptor agonist, with higher affinity towards post-synaptic at low doses and higher towards pre-synaptic at higher doses, rats did not respond to low or medium dose, they only became sexually involved at the highest dose, the reasoning is that it was 5-HT1A autoreceptor that did it.)
S15535 - it cannot be stated with beyond a doubt confidence with trials done up to this day that S15535 is working as described in this work.

Therefore we are left with pre-synaptic agonist F-13714, and F-15599 highly selective pre-synaptic 5-HT1A agonist at high dosages, they do both induce strong ejaculatory responses.
Therefore i dismiss post-synaptic 5-HT1A agonist as having something to do with PSSD, it's affinity also does not change with SSRI treatment, unlike pre-synaptic 5-HT1A.
Also look at the fact that those who got cured with treatments longer than 2 weeks had substantial reduction in symptoms even during the treatment, reasoning is that they already had agonized 5-HT1A autoreceptor during treatment, and as the treatment went on this receptor became more and more responsive. Also alcohol was taken in mushroom+MDMA and mushroom then tramadol cases, there are studies that indicate that alcohol sensitizes 5-HT1A autoreceptor.Also post-synaptic 5-HT1A activation induces anxiety, but reduces depression. What i want to do in this post is to tell people that 5-HT1A antagonists are unlikely to cure them. The possible mechanism of cure is via autoreceptor 5-HT1A agonism, sometimes very strong. Due to receptor desensitization it is also likely that 5-HT1A agonists will work on post-synaptic receptors and little to nothing on pre-synaptic receptors, until high doses of 5-HT1A agonists will be taken, they will actualy start working working on pre-synaptic 5-HT1A, it is total opposite in PSSD-free people, where 5-HT1A agonists work at first on pre-synaptic receptor and with higher doses on post-synaptic receptor.
I came to the decision to refrain from posting my treatment after reading the discussion here, i will post after i will find something that i am sure helps permanently, until then i will not make any of you my guinea pigs. Also the safety of the trial is uncertain.

https://pubmed.ncbi.nlm.nih.gov/22577236/
https://pubmed.ncbi.nlm.nih.gov/19789870/
https://pubmed.ncbi.nlm.nih.gov/22577236/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849862/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927969/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736801/
https://pubmed.ncbi.nlm.nih.gov/19094059/
https://psychedelicreview.com/binding-o ... receptors/
https://pubmed.ncbi.nlm.nih.gov/19094059/
Last edited by guacamo on Fri Sep 10, 2021 12:52 pm, edited 10 times in total.
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garycooper
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Re: I am going to drop a major bomb soon

Unread post by garycooper »

Please share your treatment and theory right now, then.
Obviously, you can sum up your treatment in 25 words, and your theory in 100 words. No need to wait for two more weeks.
Tree
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Re: I am going to drop a major bomb soon

Unread post by Tree »

Thanks for your continued research, it's much appreciated. I think many people research but we run into dead ends due to lack of research in general. Obviously the 5ht1a receptor is deeply involved with pssd, that's made apparent with many peoples negative experiences with substances that affect the 5ht1a receptor and the general theory of how ssri's are designed to work. I look forward to see if you bring any new information to the table.
cdraham
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Re: I am going to drop a major bomb soon

Unread post by cdraham »

I dont think some peoples "pssd" is related to 5ht1a /serotonin theory at all. Maybe theres different subtypes of "pssd"
Tree
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Re: I am going to drop a major bomb soon

Unread post by Tree »

cdraham wrote: Sun Aug 29, 2021 10:54 pm I dont think some peoples "pssd" is related to 5ht1a /serotonin theory at all. Maybe theres different subtypes of "pssd"
There is different degrees of pssd for sure. It is very strange though how someone can have cognitive symptoms but no sexual or sexual and no cognitive or both cognitive and sexual. I know after crashing from a 5ht1a agonist my cognitive and sexual dysfunction became severe. I assume it has to do with the differences in ssri and peoples genetics.
cdraham
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Re: I am going to drop a major bomb soon

Unread post by cdraham »

Tree wrote: Sun Aug 29, 2021 11:13 pm
cdraham wrote: Sun Aug 29, 2021 10:54 pm I dont think some peoples "pssd" is related to 5ht1a /serotonin theory at all. Maybe theres different subtypes of "pssd"
There is different degrees of pssd for sure. It is very strange though how someone can have cognitive symptoms but no sexual or sexual and no cognitive or both cognitive and sexual. I know after crashing from a 5ht1a agonist my cognitive and sexual dysfunction became severe. I assume it has to do with the differences in ssri and peoples genetics.
How can you explain the cases that are almost totally bedridden? Some 5ht1a and serotonin dysfunction wont cause insane fatigue like seen in CFS. Imo, at least for those cases we should look at what causes cfs and go from there. Corticosteroids reversed symptoms for some, this is also in complete opposite to this theory.

Maybe theres purely neurological pssd + the pssd that's more related to chronic fatigue syndrome
PsychoGenesis
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Re: I am going to drop a major bomb soon

Unread post by PsychoGenesis »

garycooper wrote: Sun Aug 29, 2021 10:41 pm Please share your treatment and theory right now, then.
Obviously, you can sum up your treatment in 25 words, and your theory in 100 words. No need to wait for two more weeks.
yeah do share it if you have sth interesting
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garycooper
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Re: I am going to drop a major bomb soon

Unread post by garycooper »

guacamo wrote: Tue Jul 13, 2021 1:08 pm I firmly believe there is 1 cause for all of PSSD, i will write final post about PSSD etiology in the upcoming days, i still do need to know a few things and i have trouble finding the correct papers.
You wrote that 7 weeks ago.....
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guacamo
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Re: I am going to drop a major bomb soon

Unread post by guacamo »

And i stand by it.
Idoagree
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Re: I am going to drop a major bomb soon

Unread post by Idoagree »

cdraham wrote: Sun Aug 29, 2021 11:30 pm
Tree wrote: Sun Aug 29, 2021 11:13 pm
cdraham wrote: Sun Aug 29, 2021 10:54 pm I dont think some peoples "pssd" is related to 5ht1a /serotonin theory at all. Maybe theres different subtypes of "pssd"
There is different degrees of pssd for sure. It is very strange though how someone can have cognitive symptoms but no sexual or sexual and no cognitive or both cognitive and sexual. I know after crashing from a 5ht1a agonist my cognitive and sexual dysfunction became severe. I assume it has to do with the differences in ssri and peoples genetics.
How can you explain the cases that are almost totally bedridden? Some 5ht1a and serotonin dysfunction wont cause insane fatigue like seen in CFS. Imo, at least for those cases we should look at what causes cfs and go from there. Corticosteroids reversed symptoms for some, this is also in complete opposite to this theory.

Maybe theres purely neurological pssd + the pssd that's more related to chronic fatigue syndrome
Are you completely bed ridden? Do you have issues with sweating?
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