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Help building a KOR-antagonistic/anti-dynorphic stack? (Depersonalization Stack)

kappa antagonist antagonism dynorphin depersonalization

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#1 formergenius

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Posted 22 September 2013 - 10:10 PM


Hello!

I've been reading about the involvement of the Kappa Opioid Receptor in Depersonalization, which alas I do have.
I'll skip the drama about how I got it and how much it sucks, and get to the point. If this is still too lengthy, please scroll down to "Help needed".

Concurrently with the DP, I also have brainfog, which seems more like borderline-dementia. This makes it hard (and ironic) for me to study how to fix this, which is why I'm asking for help here. I'll continue looking into it myself, but I figured if anyone has any ideas/pre-existing knowledge here, it would obviously help the process.

Turns out that basically what I want to do is antagonize my KOR's. Considering that Naloxone is highly unsustainable, and Naltrexone is hard to come by and also not exactly favorable, I need to find another way. JDtic, Nor-binaltorphimine, 5'-Guanidinonaltrindole, and TENA are all KOR antagonists, but these are all currently unavailable, let alone their safety information.

One drug in particular that will be available in my country shortly is Nalmefene, which I will try when I can. However, I rather not wait around until that happens. Moreover it's not a specific antagonist, though I suppose I could live with that. Beggars can't be choosers, right?

Current stack:
Currently I'm taking 500mg Levetiracetam BID for my HPPD, which I'll be dropping soon because it has done absolutely nothing for me. I figured for now I should nevermind the visual distortions and focus on alleviating cognitive dysfunction, depersonalization, anxiety and depression.

I also more or less take the following supplements daily: Magnesium Malate (1-2 grams), 4-5ml NOW sublingual B-complex, 5000IU vitamin D3, and Source of Life Gold Multi-Tabs at 6 tablets OD. I use Cannabidiol and Damiana as needed for sleep.

Prospective substances:
Anyhow, I came across the substance Amentoflavone, which is found naturally in St. John's Wort and Ginkgo Biloba, and appears to be a KOR antagonist (also an antagonist at another opioid receptor, but I forgot). So I've ordered top-quality brands of the stuff (Perika SJW, Ginkgold Ginkgo). I've never even tried SJW, so I think it's worth a shot regardless of its amentoflavone content (could help with co-morbid issues). I'd tried some supermarket brand Ginkgo last year, which didn't help, but after reading this thread I decided to give it another shot. Also.. Curcumin. Damn I already forgot how it would be helpful exactly, but it should somehow help. I'll update once I read through it again.

Help needed:
I came across all kinds of terms I'm unfamiliar with, mainly (m)CREB and cAMP. I've read up a bit about (neuro)endocrinology (thank you Sapolsky), yet alas I've forgotten most about that too. Guess I should go through my notes again. In any case; CRF/CRH seems to be involved as well w.r.t. dynorphin production. And along these lines I get overwhelmed, so here is where I ask for help.

Can anyone point me to solid literature about these processes and how they're involved with KOR's and Dynorphin? Specifically CREB and cAMP literature (where do I begin?). Moreover, does anybody know how, via these mechanisms or not, to induce/support the desired effect (as stated in the thread title)? Or really just anything that could help me further this idea and/or your own inputs?

Many thanks in advance!

#2 celebes

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Posted 23 September 2013 - 12:15 AM

Amentoflavone is removed from Ginkgold and, I believe, most other standardized formulations. So no luck there.

The only ways to antagonize KOR orally apart from JDtic would be ALKS 5461 or a combination of buprenorphine and naltrexone/naloxone.

Kappa agonism to downregulate KOR should work in theory but the research points to it being more complicated than straight antagonism. Salvia does indeed work and has for me but at the same time but can itself cause lasting depersonalization. Hesperidin is another agonist for anyone who wants to go down that route.

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#3 MercuryAX

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Posted 23 September 2013 - 02:35 AM

Formergenius -

Hi there, and thank you for posting in my topic regarding this as well. You were asking about the cAMP, so you might want to check this out:
http://corpina.org/c...zing-potential/

#4 formergenius

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Posted 23 September 2013 - 12:14 PM

celebes:
Yes I feared it to be so, so it comes as no surprise. I want to try this combo regardless, so no regrets buying it. Alas; Amentoflavone is not commercially available, unless it's bulk from China.
Indeed I might try Suboxone as a one-time experiment, to see how that effects me. Though bupenorphine is a partial agonist at MOR's, and an antagonist at both Delta and Kappa sites, correct? Not sure about how desirable this profile is.. perhaps low-dose Suboxone is worth a shot, but afaik it has addictive properties, no?
My intentions of this thread was more or less to find a way to "indirectly" antagonize KOR and/or Dynorphin production, which should lead to the same results, or so I presumed.

MercuryAX: Thanks for that link! I've seen mentions of the CILTEP stack floating around a lot, but never really looked in to it. I'll check it out further, as I'm not sure as increasing cAMP would be beneficial to this cause. Taking the addiction model, it would seem that increasing cAMP would lead to increasing PKA, which would lead to CREB activation, which would lead to increased Dynorphin expression, which would agonize KORs and also decrease DA release.
That's just from an initial glance though; I might've misinterpreted it. Oh well, I'll keep reading and I'm sure I'll understand it at some point.

#5 celebes

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Posted 23 September 2013 - 05:52 PM

Indeed I might try Suboxone as a one-time experiment, to see how that effects me. Though bupenorphine is a partial agonist at MOR's, and an antagonist at both Delta and Kappa sites, correct? Not sure about how desirable this profile is.. perhaps low-dose Suboxone is worth a shot, but afaik it has addictive properties, no?
My intentions of this thread was more or less to find a way to "indirectly" antagonize KOR and/or Dynorphin production, which should lead to the same results, or so I presumed.


All the answers you're looking for are somewhere in these threads:

http://www.longecity...tionwithdrawal/
http://www.longecity...-bulkgroup-buy/

If you read through them you would understand how suboxone on its own is ineffective, as well as the few ways to indirectly antagonize KOR.

#6 formergenius

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Posted 23 September 2013 - 06:59 PM

Thanks celebes, I'll read through those with more scrutiny. I saw one post in particular about combining Buprenorphine+Naltrexone in specific ratios to mitigate addiction/tolerance potential, was it yours? Sure I'll come across it when I read through those threads again.

Psyched about the JDtic though!

#7 KieranA001

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Posted 05 November 2013 - 04:04 PM

May I ask, has the Ginkgold Ginkgo helped you at all? I was thinking of getting some because it apparently increases blood flow to the brain and other parts of the body. Seen as anxiety causes the body to draw more blood to the lungs I would think it should help ??

#8 celebes

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Posted 05 November 2013 - 06:19 PM

Ginkgo/Ginkgold is a 5-ht1a agonist, which would be the main anxiolytic mechanism. It also increases/preserves DA transmission and BDNF. It does something to cortisol too, possibly indirectly.

It has helped me a lot, personally. One of the absolute best in my experience. If they didn't remove the amentoflavone, it would really be gold...

Edited by celebes, 05 November 2013 - 06:20 PM.

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#9 KieranA001

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Posted 05 November 2013 - 07:07 PM

Ginkgo/Ginkgold is a 5-ht1a agonist, which would be the main anxiolytic mechanism. It also increases/preserves DA transmission and BDNF. It does something to cortisol too, possibly indirectly.

It has helped me a lot, personally. One of the absolute best in my experience. If they didn't remove the amentoflavone, it would really be gold...


Thanks for the insight. Couldn't you just buy the amentoflavone seperately ? :-)

More to the point, why did the remove it in they first place :/

Edited by KieranA001, 05 November 2013 - 07:07 PM.


#10 KieranA001

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Posted 05 November 2013 - 07:37 PM

Just out of curiosity. Is there any difference between Ginkgo Gold and this:

http://www.ebay.co.u...=item27d5219f4d

Apart from the fact it's cheaper and has more Ginkgo in it. ??

#11 celebes

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Posted 05 November 2013 - 10:25 PM

With Ginkgold (Egb 761) you know what you're getting. I can't believe that anything at £4 would be legit. But there's nothing to lose by trying it at that price.

#12 socialpiranha

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Posted 13 November 2013 - 09:13 PM

amentoflavone is probably anxiogenic as it is a negative modulator at the gaba a receptor as well as an antagonist at the mu and delta receptor in addition to the kappa receptor...

http://www.ncbi.nlm....pubmed/12824018

#13 KimberCT

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Posted 13 November 2013 - 11:44 PM

Ginko, including Ginkgold, always gives me terrible anxiety. Panic-type physical anxiety. It feels very similar to the anxiety I experienced when trying SJW. I blamed the amentoflavone content, but if it is removed from Ginkgold..... anyone hazard a guess as to what could be causing the anxiety?

#14 celebes

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Posted 14 November 2013 - 11:18 AM

They both increase serotonin levels. A physical anxiety is one of the symptoms of serotonin excess.

GABA A modulation might not be entirely negative: it's anxiolytic in vivo. But it's not supposed to cross the BBB well?
http://www.sciencedi...091305712002389

The GABA effect seems to be more prominent than any opioid activity it has.

Edited by celebes, 14 November 2013 - 12:13 PM.


#15 VERITAS INCORRUPTUS

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Posted 28 February 2014 - 04:06 PM

They both increase serotonin levels. A physical anxiety is one of the symptoms of serotonin excess.

GABA A modulation might not be entirely negative: it's anxiolytic in vivo. But it's not supposed to cross the BBB well?
http://www.sciencedi...091305712002389

The GABA effect seems to be more prominent than any opioid activity it has.


Amentoflavone is antagonist at GABA-A, so therein potentially stimulating, anxiogenic, and even potential for tremogenicity.
Though, again, it is not in the extract so denoted.

#16 socialpiranha

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Posted 28 February 2014 - 04:32 PM

here's a study which seems sort of counterintuitive but suggest amentoflavones antagonistic effects on the gaba receptor mediate its anxiolytic effects.

http://www.ncbi.nlm....pubmed/22944105

Edit: just realized celebes just posted that link ha sorry and that it's a different (agonist) mechanism rather than its antagonistic effect which facilitates the anxiolytic effect. Apparently it has all kinds of wacky effects on the gaba receptor

Edited by socialpiranha, 28 February 2014 - 04:47 PM.


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#17 Flex

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Posted 04 April 2014 - 08:27 AM

There is a involvement of Natrium/Sodium channels in opioid function:

Scientists Solve 40-Year-Old Salt Mystery

http://www.laborator...efined&at_pos=0

Edited by Flex, 04 April 2014 - 08:27 AM.






Also tagged with one or more of these keywords: kappa, antagonist, antagonism, dynorphin, depersonalization

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