Postsynaptic 5HT1AR: worth re-exploring (trial)

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Meso
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Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Meso »

I've been reading a bit on Saint John's Wort (SJW) as it remains to be an enigmatic substance. There is no clear study on how it works. It seems that hyperforin mediates the neurotransmitter releasing property of it while Hypericin is even less researched than hyperforin and affects MAO, NMDA, PKC, and DBH. It also interacts with mu opioid receptors.

I've also been reading up on threads here of people who trialed it and noticed that most people never gave it a proper trial (short duration / low dose).

Blunted affect remains to be the last symptom I'm having and it's quite elusive. The entactogen effect of many serotonin releasing agents is mediated mainly by activation of postsynaptic 5HT1A receptors, so I'm mainly interested in its ability to upregulate said receptors. Some people allegedly use SJW to restore MDMA's entactogen effects. It might as well be placebo, but I'm going to try it regardless.

The only time I tried SJW myself was during the Vortioxetine trial in an effort to offset the 5HT1A downregulation - but I wouldn't call that fair as Vortioxetine is a quite potent 5HT1A agonist with high affinity (15 nM) and intrinsic activity (96%).

My current state:
Sexual functions: 9/10 (mild numbness left)
Hedonic function: 7-9/10 (depends on sleep quality)
Cognitive functions: 7-9/10 (some brainfog, same as above)
Emotional function: 2/10 (severe emotional blunting)

I can only feel basic emotions and even those are relatively mild in intensity. There are some substances that can restore emotions for a short duration of time, but those are more like band-aids (not suitable for long-term use).

I'm designing a fair trial of SJW. First, I want to take SJW (3% hyperforin extract) for several months. If that doesn't work well, I'll switch to a high hypericin extract for some more months. This is, of course, while taking the rest of my regimen as long as there aren't any drug-drug interactions.

I'm still contemplating the design.
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Leb89
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Leb89 »

Hey Meso,

Can you explain how you fixed your sexual function to 90 %? That would be amazing

Cheers,
Leb.
Thomas
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Thomas »

Leb89 wrote:
Mon Aug 17, 2020 7:53 am
Can you explain how you fixed your sexual function to 90 %? That would be amazing
cf. viewtopic.php?t=2863

@Meso: regarding your emotional bluntness (worst symptom for me, because I feel my loss of libido and anhedonia both come from feeling nothing), you had some results... which did not last?
Escitalopram, 10mg/day, Jan-May 2019. Fluoxetine, May-Sept 2019. Mirtazapine, November 2019-January 2020. Escitalopram, Feb-May 2020.
Symptoms: loss of libido | anhedonia | sexual numbness
Semogomes
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Semogomes »

@meso do you still have pramature ejaculation?

I'm dealing with this and the other symptoms:

-10% libido
- big ED
- 50% penis sensitivity
- soft glands
- anhedonia and emotional blunting

I took venlafaxine 37.5mg for 3 days almost 2 months ago and quitted it rapidly. Was taking Amitriptiline along, 25mg and was having no problems with erection, that's why I started Bupropion, that restored my orgasms but made me get ED. Took Amitriptiline for 2 months and bup for 2 weeks.

Left all meds 2 weeks ago and zero improvements till now, only developed PE after quiting them. Any advice? I'm thinking of trying Lithium orotate and ginseng
Trazohell
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Trazohell »

We have discussed St. John's wort a thousand times before, it seems to be helpfull for only a few lucky ones (if the storys are true) but can also make you worse or even give you PSSD (anecdotal reports).
June 2015 - April 2016 Fluoxetine
April 2016 - March 2017 Fluvoxamine
December 2017 9 days Trazodone
After Trazodone PSSD: loss of libido & spontaneous/night/morning erections, prostate/pelvic pain, genital numbness, lower sperm count, Anhedonia
Trazohell
Posts: 179
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Trazohell »

Somewhere you wrote that you don't believe in 5HT1 desensitation theory?
June 2015 - April 2016 Fluoxetine
April 2016 - March 2017 Fluvoxamine
December 2017 9 days Trazodone
After Trazodone PSSD: loss of libido & spontaneous/night/morning erections, prostate/pelvic pain, genital numbness, lower sperm count, Anhedonia
Halan
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Halan »

What about buspirone? Some people got better using it.
viewtopic.php?f=20&t=3559
and
viewtopic.php?f=41&t=3480
Benji19912
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by Benji19912 »

I’m confused, meso’s last recovery experiment involving DXM ended up being a failure but he has posted very good scores here for his pssd symptons, did he change his regimen?
fellow1
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by fellow1 »

Be careful. Hypericin is proved to cause cataracts if exposed to sun/light. And SJW generally is associated with cataract. Many studies on this.
Previous studies have shown that hypericin can photosensitize lens proteins in vitro [21], can cause cataracts in UV exposed excised bovine lenses [12] and can induce cell death in human lens epithelial culture
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654046/
PsychoGenesis
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Re: Postsynaptic 5HT1AR: worth re-exploring (trial)

Unread post by PsychoGenesis »

Benji19912 wrote:
Mon Aug 17, 2020 6:26 pm
I’m confused, meso’s last recovery experiment involving DXM ended up being a failure but he has posted very good scores here for his pssd symptons, did he change his regimen?
it was a failure in terms of curing PSSD as a whole and blunted affect but his sexual improvements sticked

i did that combo(both low and high dose) a try for periods shorter than 2-3 weeks, but it's not so simple

fellow1 wrote:
Mon Aug 17, 2020 8:09 pm
Be careful. Hypericin is proved to cause cataracts if exposed to sun/light. And SJW generally is associated with cataract. Many studies on this.
Previous studies have shown that hypericin can photosensitize lens proteins in vitro [21], can cause cataracts in UV exposed excised bovine lenses [12] and can induce cell death in human lens epithelial culture
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654046/
yeah, lets not go out sun gazing on hypericin people
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