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Ferulic acid, a natural NMDA antagonist and serotonergic antidepressant

ferulic acid nmda ht1a ht2a ht2c

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#61 sativa

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Posted 25 May 2016 - 02:56 PM

Basically you use tryptophan as a Tryptamine precursor. That's it! Nudge the enzymes to ensure more tryptophan is turned into Tryptamine using phenylalanine or 5htp.

#62 gamesguru

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Posted 25 May 2016 - 03:24 PM

Bacopa and lithium upregulate TPH2.

Phenylalanine is a dopamine, not serotonin, precursor.
You could inhibit TH, but this would not affect the competition for absorption at the BBB between tryptophan and tyrosine, so you may as well anyhow take TH promoters (e.g. horny goat weed), and just really monitor dietary protein and, of course, supplement tryptophan. That way you could ration, for example, tyrosine, while still hopefully ensuring adequate dopamine turnover.

Edited by gamesguru, 25 May 2016 - 03:24 PM.


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#63 sativa

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Posted 25 May 2016 - 06:01 PM

Interesting!

Imagine taking a small dose of memantine (perhaps 10mg) and having its effects last for days!

Well with cycling that's possible.

I guess this would save money because this unconventional method doesn't require you to constantly redose the substance (in this case memantine).

But cycling will, of course, affect the metabolism of any other things you take (and prolong their action too) so this could cause complications.

Cycling requires aldehyde dehydrogenase inhibition. Perhaps taking extra antioxidants, SOD boosting supplements and having a healthy dopamine system to help neutralize the effects of built up potentially toxic metabolites such as DOPAL.

Also, you could just have "short bursts" of ALDH inhibition to minimise DOPAL accumulation.

Pomegranate extract is a great option for ALDH inhibition, as are almond extract (benzaldehyde), cinnamon oil (cinnamaldhyde), anise oil (anisaldehyde)

Edited by sativa, 25 May 2016 - 06:10 PM.


#64 normalizing

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Posted 25 May 2016 - 10:22 PM

too much stuff is starting to get thrown in there. gonna become some kind of supplemental machine to keep up with supply and demand. until there is a way to figure out this as sustainable basic mix that works, the idea of just using some ayhuasca in comparison seems easier



#65 sativa

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Posted 26 May 2016 - 12:01 AM

Lol? This mix and it's mechanisms were established years ago.

Its basic stuff man - at its core:

Pomegranate (ALDHi), black pepper/lysine/choline (for piperidine/dimethylamine) and your desired alkaloid.

Thats a pretty basic mix.

Any aldehyde functions as an ALDH inhibitor so the more the merrier.

You say the idea of using conventional ayahuasca might seem preferable, but this doesn't apply to explorers who might wish to explore the unknown and experience totally new novel compounds.

Also, ayahuasca is (generally) limited to a DMT style experience. Think bigger normalising!! Expand your horizons...

Cycling applies to most substances (piracetam, phenibut, modafinil, salvia, kanna, cannabinoids, etc)...and allows for indefinite effects ;) The question is whether your mind and body is capable of withstanding such an experience.

Edited by sativa, 26 May 2016 - 12:11 AM.


#66 gamesguru

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Posted 26 May 2016 - 12:22 AM

cue proadifen and grapefruit juice

Edited by gamesguru, 26 May 2016 - 12:23 AM.

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#67 normalizing

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Posted 26 May 2016 - 01:41 AM

so all of sudden pomegranate is thrown in there... interesting kind of missing last 2 pages



#68 sativa

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Posted 26 May 2016 - 11:12 AM

cue proadifen and grapefruit juice

Not really, their methods of action are not required in anyway shape or form.

so all of sudden pomegranate is thrown in there... interesting kind of missing last 2 pages

What are you trying to imply (Lol)
From page 2:

Why don't you try and make Phenylethylpiperidine in vivo using legal food based ALDH inhibitors....

That covers pomegranate, cinnamon, anise seeds, bitter almonds etc

Normalising, you're chasing nonexistent ghosts!

Edited by sativa, 26 May 2016 - 11:20 AM.


#69 sativa

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Posted 26 May 2016 - 11:16 AM

D.p

Edited by sativa, 26 May 2016 - 11:16 AM.


#70 gamesguru

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Posted 26 May 2016 - 11:18 AM

They work just as well to inhibit liver enzymes? They might even exten an acid trip

#71 sativa

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Posted 26 May 2016 - 11:24 AM

They work just as well to inhibit liver enzymes? They might even exten an acid trip


Yes, but for cycling, only enzymes that metabolise aldehydes need to be inhibited.

#72 sativa

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Posted 26 May 2016 - 11:37 AM

Bacopa and lithium upregulate TPH2.

Phenylalanine is a dopamine, not serotonin, precursor.
You could inhibit TH, but this would not affect the competition for absorption at the BBB between tryptophan and tyrosine, so you may as well anyhow take TH promoters (e.g. horny goat weed), and just really monitor dietary protein and, of course, supplement tryptophan. That way you could ration, for example, tyrosine, while still hopefully ensuring adequate dopamine turnover.

I've just reread this and I see now, tryptophan and tyrosine (tyrosine being created from phenylalanine) will compete for absorption. Hmm

(To force L-tryptophan to be converted to tryptamine, you need to inhibit tryptophan 5-monooxygenase, inhibitors include phenylalanine and 5-HTP)

Edited by sativa, 26 May 2016 - 12:30 PM.


#73 gamesguru

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Posted 26 May 2016 - 12:18 PM

If that is your goal an MAOI might also help trip you out. That enzyme has a sweet tooth for tryptamine.

As far as phenykalanine being a precursor to tryotophan, references please.

"As an essential amino acid, tryptophan is not synthesized from more basic substances in humans and other animals, who must ingest tryptophan or tryptophan-containing proteins..."

#74 sativa

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Posted 26 May 2016 - 12:39 PM

If that is your goal an MAOI might also help trip you out. That enzyme has a sweet tooth for tryptamine.

As far as phenykalanine being a precursor to tryotophan, references please.

An MAOi would only be required for N-methylated tryptamine. [I take this back, see EDIT at end of post]

When creating piperidine analogues of DMT for example, MAO enzymes don't touch it. The same goes for the piperidine analogue of PEA.

MAO's appetite for the newly formed molecule would totally depend on it's structure. Who knows what MAO thinks of the piperidine/dimethylamine analogue of memantine/mesembrine/ibogaine/harmaline etc?! All very novel likely unresearched compounds...

Oh that tryptophan/phenylalanine thing was a wording error on my part, I only meant tyrosine from phenylalanine. Fixed it.

\\EDIT//
Pomegranate extract potently inhibits aldehyde dehydrogenase, aldose reductase, and xanthine oxidase.

It would seem that MAO is necessary and crucial for cycling to work, as it produces the aldehydes that then bind with piperidine/dimethylamine:

As everyone knows, DMT is hacked away by MAO and turned into indoleacetaldehyde, and then quickly becomes indoleacetic acid by the action of aldehyde dehydrogenase. However, because of the aldehyde dehydrogenase inhibitor, some of the DMT will be reincarnated from indoleacetaldehyde over and over until something other than MAO attackes it.


Edited by sativa, 26 May 2016 - 01:00 PM.


#75 normalizing

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Posted 26 May 2016 - 02:31 PM

sativa mind me asking, whats your education in biochemistry



#76 sativa

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Posted 26 May 2016 - 02:40 PM

AS level biology at school, the rest is self taught.

A long period of Piracetam (and a few other substances) seems to have permanently enhanced rate of learning and ability to understand and contextualise new concepts and information. Coupled with a burning passion for relevant knowledge means learning becomes fun, more effective and easier.

Edited by sativa, 26 May 2016 - 02:42 PM.

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#77 ULTRA_VULGAR

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Posted 26 May 2016 - 05:22 PM

That's amazing. Thanks so much for putting FA on my radar. Sativa, in your experience, is this something you would consider taking as part of a daily regimen? If so, at .55 g or a lower threshold? If not, would you recommend limiting FA use to 1-2 times a week? I can't see anything in those studies that indicates either way.  

Newb question: Does the trans isomer of ferulic acid share these attributes? trans-FA is all I can find at the moment. 



#78 sativa

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Posted 26 May 2016 - 05:33 PM

I don't see why this couldn't be taken as part of a daily regimen.

I based my dosage on the amount in each capsule of the Trans-Ferulic acid products.

I've just done some quick googling and it seems these are all different names for the same thing:

Ferulic acid
Trans-Ferulic Acid
4-Hydroxy-3-methoxycinnamic acid
Trans-4-Hydroxy-3-methoxycinnamic

Edited by sativa, 26 May 2016 - 05:37 PM.


#79 gamesguru

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Posted 02 June 2016 - 10:47 PM

Ferulic acid (FA) is an abundant dietary antioxidant which may offer beneficial effects against cancer, cardiovascular disease, diabetes and Alzheimer’s disease. The impact of FA on health depends on its intake and pharmacokinetic properties. In this article, the literature pertaining to chemistry, natural sources, dietary intake and pharmacokinetic properties of FA is critically reviewed. High levels of FA are found in both free and bound forms in vegetables, fruits, cereals, and coffee. We have estimated that consumption of these foods may result in approximately 150–250 mg/day of FA intake. FA can be absorbed along the entire gastrointestinal tract and metabolized mainly by the liver. The absorption and metabolism of FA seem to be dose dependent at least in experimental settings. Further pharmacokinetic and pharmacodynamic studies are required to characterize the impact of FA on human health.

 

about 50% of FA reaches the liver, and the remainder is distributed in the bloodstream, gastric mucosa and peripheral tissues. Chang et al. (1993) administered pure FA in Wistar rats and found that the free acid did not enter the enterohepatic circulation. Conjugation was required for its distribution in the organism. The conjugation reactions of FA occur mainly in the liver but may also occur in the intestinal mucosa or kidney, catalyzed by sulfotransferases (EC 2.8.2.1) and UDP glucuronosyl transferases (EC 2.4.1.17). Studies in humans and rats showed that after oral intake of FA, the most abundant metabolites generated in plasma were FA-glucuronide (FA conjugate with glucuronic acid) and FA-sulfoglucuronide (FA conjugate with sulfate and glucuronide) in addition to unmodified FA. The studies indicated that concentrations of metabolites derived from FA ingestion are a function of several factors such as the dose and route administered, as well as the animal species.

 

Ferulic acid (FA), a ubiquitous natural phenolic phytochemical present in seeds, leaves, both in its free form and covalently conjugated to the plant cell wall polysaccharides, glycoproteins,polyamines, lignin and hydroxy fatty acids. FA plays a vital role in providing the rigidity to the cell wall and formation of other important organic compounds like coniferyl alcohol, vanillin, sinapic, diferulic acid and curcumin. FA exhibits wide variety of biological activities such as antioxidant, antiinflammatory, antimicrobial, antiallergic, hepatoprotective, anticarcinogenic, antithrombotic, increase sperm viability, antiviral and vasodilatory actions, metal chelation, modulation of enzyme activity, activation of transcriptional factors, gene expression and signal transduction.


Edited by gamesguru, 02 June 2016 - 10:50 PM.


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#80 sativa

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Posted 02 June 2016 - 11:06 PM

Thanks for that info.

Btw, Ferulic acid tastes like chalky vanilla, but soon this taste becomes somewhat unpleasant..the "novelty wears off" shall we say.

Edited by sativa, 02 June 2016 - 11:07 PM.






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