Lately I've been examining the causes - the actual definitive (original) causes of the disorder known as "PSSD" or Post-SSRI sexual dysfunction; though this also applies to other antidepressants that increase Serotonin - it appears that there is some merit to the following theories...
- Androgen Receptor downregulation theory; that SSRI antidepressant reduce the 'receptors' or keyholes for Hormones - needed to work properly [study].
- 5-HT1A "desensitization"; partly - though not the CORE issue. [research]
- Nitric Oxide downregulation; *definitely*; but again, more complicated than this.
- Nerve Deterioration; caused by above issues! [also epigenetic issues]
- NeuroSteroid alterations; bullshit theory (in-part)...but Pregnenolone may help! [see here]
The real theory that works here is what I found recently...the drug manufacturers (after talking with them) were actually UNAWARE of this...its actually a Mechanism of permanent sustenance of the 5-HT1A post-synaptic (right-side) receptor that "cuts off" the PPAR --> Androgen Receptor --> nNOS connection. It appears that "nuclear receptors" are in control (and governance) of sexual function - and that disruption of them by SSRI's and other antidepressants - this is the real cause of PSSD. [2019 Research Paper].
There may be however...a way around this - and it revolves around THREE strategies...
- Take DXM (dextromethorphan) or Memantine to upregulate the NMDA-receptors; to restore the Nitric Oxide pathway. [study 1] [study 2]
- Take Risperidone; an antipsychotic for 1-week to upregulate the Dopamine D2-receptors; as they are needed for erections etc [upregulation study] [D2 & Erections]
- Find a source and buy LECOZOTAN - a unique 5-HT1A antagonist which should block the post-synaptic receptors and restore nerve sensations and spinal connections.
ANDROGEN's Recruit Neuronal Nitric Oxide Synthase in a Specific Manner
Androgen's are the key ingredient for masculinity, though they are often depreciated due to media attacks on manhood & persistent chemical attacks, the LGBT society/movements and other realms of dissonance against "all that is man".
However, there are two types of masculinity. There is...
- Old-World (traditional) Masculinity; that is, that a Man is defined by his actions; his bravery, his efficient defending of his Family - being righteous, strong, charismatic & having good leadership skills - one who is the 'breadwinner' - takes care of tough chores and does things that aim to inform & teach. Masculinity in the "old-world sense" is described as being Assertive/Dominant, Action-oriented and Bold.
- New World Masculinity; new world masculinity is defined by being hypersexual, making a girl/mate cum the most (orgasms) and being rough, tough, even brutal. This type is more common in City (urban) area's and Ghetto's...but is increasingly accepted (and apparent) even within circles of the Rich.
Although Testosterone & DHT provide the initiation and continuing release of these messengers; they are wholly separate from each other - and WITHOUT blocking the Androgen's - you can 'disrupt' the nNOS portion of this and will still result in a ceasing (stopping) of sexuality and sexual behavior. Thus, sexual behavior and being hypersexual or even a "player" is dependent on nNOS (nitric oxide)...
Some *keys* about "nNOS"...
- nNOS is the "nerve-based" or nerve released nitric oxide - so like when you get a boner from being around a female (girl) - and its automatic, meaning you don't touch yourself or even touch your Dick to anything - yet it goes up (gets hard) - that IS because the NERVES are responding to electrical impulses from the Brain - thus, the electrical nerves TELL the arteries in the Penis to dilate by sending an "electric command" to Do So.
- nNOS is different from the type of Nitric Oxide found in the Heart and other blood vessels; it also plays a HUGE role in Behavior; it initiates Sexual Behavior (SB) [1] and sex drive [2] [3] [4] - but it also leads to stimulation/awareness/vigilance [5], memory formation [6] and Depression (in high amounts) [7].
- However, iNOS and nNOS can also *promote* sleep/sedation [8].
- LOW nNOS in the LCN (Locus Coeruleus) causes Depression, as well, however [9].
- Dopamine causes Erections via D2-receptors [10] [11] [12] and nNOS pathways [13]. It does this by activating the SPINAL Oxytocin receptors [14].
:::SEROTONIN AND THE ANDROGEN RECEPTOR:::
How Does Serotonin affect/reduce Testosterone?
Serotonin downregulates GnRH (Gonadotropin Releasing Hormone) [15] - this hormone is the "Master Switch" which tells the testicles/ovaries to create hormones (Testosterone & Estrogen).
Serotonin reduces GnRH by reducing the "messenger" activities (electrical messages)...
5-HT (Serotonin) *also* downregulates the AR (androgen receptor) by reducing cAMP formation via 5-HT1A & 5-HT1B receptor activation. Thus, a useful theory that could be used to prevent/treat PSSD is to block the 5-HT1A & 5-HT1B heteroreceptors - the ONLY way to do that - is to take a Supplement called Wild Jujube Extract [!] - you can also take it with METERGOLINE - a drug used to block serotonin receptors. [buy Metergoline online 2019] (buy MET here).
You can use a Supplement called Forskolin (coleus forskohlii extract) in order to prevent Androgen Receptor blockade (naturally) [2019].
Serotonin when reinforced by SSRI's - tends to also reduce genetic expression of proteins that control sex hormones [16] [17]. They reduce the mRNA of GnRh [18]. This couples to my theory that there is a central hormonal dysregulation on both a genetic & receptor level [18] [19], induced by SSRI's [20]. Since serotonin can have differing effects itself [21], its postulated that the overwhelming additional serotonin can activate more suppressive pathways than initiatory pathways. There are, after all - multiple signals such as the "second messenger" pathways (cAMP/cGMP) that can be suppressed by antidepressants [22] [23] [24] [25].
You can use a Supplement called Forskolin (coleus forskohlii extract) in order to prevent Androgen Receptor blockade (naturally) [2019].
Serotonin when reinforced by SSRI's - tends to also reduce genetic expression of proteins that control sex hormones [16] [17]. They reduce the mRNA of GnRh [18]. This couples to my theory that there is a central hormonal dysregulation on both a genetic & receptor level [18] [19], induced by SSRI's [20]. Since serotonin can have differing effects itself [21], its postulated that the overwhelming additional serotonin can activate more suppressive pathways than initiatory pathways. There are, after all - multiple signals such as the "second messenger" pathways (cAMP/cGMP) that can be suppressed by antidepressants [22] [23] [24] [25].
5-HT1A & 5-HT1B receptors decrease Androgen Receptors by THREE pathways...
PPARy reduction --> study --> https://www.ncbi.nlm.nih.gov/pubmed/25937083
Reduction of cAMP (cyclic adenosine monophosphate) --> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121227/
cAMP/PKA and Androgen Receptors --> https://www.ncbi.nlm.nih.gov/pubmed/8702703
Reduction of nNOS --> less blood flow --> less Androgen Receptor "food" or nourishment --> https://gut.bmj.com/content/44/2/143 [study 2] [study 3]
Reduction of nNOS = chemical castraction --> https://www.ncbi.nlm.nih.gov/pubmed/21506911
My PSSD post on PSSDforum.com...
The cause of PSSD has had many theories, but I'm going to skip to the chase.
The REASON we CAN'T treat PSSD *(effectively)* is because we are Obsessing on theories that only "HINT" at one point of the problem.
Where does "the point" originate from, though?
I believe I've found the answer...
It lies in PPARy or "Peroxisome proliferator-activated receptor gamma".
--> Serotonin REDUCES PPARy which normally ACTS to INITIATE Androgen Receptor (AR) activities; that's *WHY* we get DOWNREGULATION of androgen receptors with SSRI - because the "nuclear" receptor of PPARy is being downregulated (persistently) by SSRI's - which causes a continual reduction in Androgen Receptor amounts (densities) and activities. SSRI's like Luvox & Prozac "get in the middle" and cut off the "supply and demand" connection to nNOS from the Androgen Receptor - leading to LESS neuronal nitric oxide synthase and *NO* non-contact erections (erections without touch). STUDY --> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641178/
--> PPAR stimulates Androgen Receptors and activities --> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428145/
5-HT1A & 5-HT1B receptors REDUCE androgen receptors as [b][color=#FF0000]MESOLIMBO[/color][/b] has So Said.
5-HT regulates PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA PPAR/PPARy --> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957204/
5-HT1A & 5-HT1B receptors do this via THREE pathways...
PPARy reduction --> study --> https://www.ncbi.nlm.nih.gov/pubmed/25937083
Reduction of cAMP (cyclic adenosine monophosphate) --> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121227/
cAMP/PKA and Androgen Receptors --> https://www.ncbi.nlm.nih.gov/pubmed/8702703
Reduction of nNOS --> less blood flow --> less Androgen Receptor "food" or nourishment --> https://gut.bmj.com/content/44/2/143 [study 2] [study 3]
Reduction of nNOS = chemical castraction --> https://www.ncbi.nlm.nih.gov/pubmed/21506911
Reduction of nNOS = chemical castraction --> https://www.ncbi.nlm.nih.gov/pubmed/21506911
***FORSKOLIN may also PREVENT FLUTAMIDE and other ANTI-ANDROGENS FROM BINDING/WORKING***
***MORE EVIDENCE***
PPAR is involved in LEVODOPA induced DYSKINESIAS - a "symbol" of how WELL Dopamine works in the FACE less PPARy (IT DOESN'T!!!)
STUDY --> https://www.ncbi.nlm.nih.gov/pubmed/25486547
***GENETICS***
nNOS contributes to STRESS-induced Depression --> https://www.ncbi.nlm.nih.gov/pubmed/17854383
SOME PEOPLE have GENEs that make them have *MORE* or *LESS* neuronal nitric oxide Synthase --> https://www.ncbi.nlm.nih.gov/pubmed/20888049
nNOS is *LOW* in the LOCUS COERULEUS --> https://www.ncbi.nlm.nih.gov/pubmed/15569249
***EXPLORING SCIENTIFICALLY PROVEN APHRODISIACS***
Exploring scientifically proven herbal aphrodisiacs [STUDY] --> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731873/
Arch Gen Psychiatry. 1989 Mar;46(3):275-84.
Effects of psychotropic drugs on human erection and ejaculation.
Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. (NATURE)
Mol Psychiatry. 2014 Oct;19(10):1106-14. doi: 10.1038/mp.2013.144. Epub 2013 Oct 29.
Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. (NATURE)
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363657/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995787/
https://www.ncbi.nlm.nih.gov/pubmed/20888049
https://www.ncbi.nlm.nih.gov/pubmed/29181019
https://www.ncbi.nlm.nih.gov/pubmed/17971830
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363657/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995787/
https://www.ncbi.nlm.nih.gov/pubmed/20888049
Very interesting post !!
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To pour fire in the intrigue http://www.pssdforum.com/viewtopic.php?f=5&t=3195#p31019
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671492/
that INCREASING serotonin reduces glycogen accumulation!
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DeleteOP, How to increase nNos? and concerning the Risperidone. You said to take it for 1 week, but at what dosage?
ReplyDeleteThank you.
Hello OP??
DeleteI didn't expect anyone taking this part seriously in the first place, but since you ask: Taking Risperidone according to this advice is the most ludicrously reckless thing one can. Risperidone is one of the most side-effect heavy medication in existence, and that includes sexual eradication just very low down on the list. Also, there is hardly a receptor in the human body it doesn't antagonise, so thinking it would be good just as a 5HT2a antagonist, is absolutely deranged. Oh, and: I am just interested in the issue (and something perhaps more severe) BECAUSE of Risperidone...
DeleteHi there, do any supplements exist or safe medications that delay ejaculation ? I do not want to take SSRI's.
ReplyDeleteAntihistamine's such as Benadryl, or Dapoxetine are really the only options.
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