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Pepper Activity Tests (it inhibits CYP1A2, CYP3A4, and CYP2D6)

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69ron

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#21 [url]

Jun 29 08 1:05 AM

However I haven`t find any info about the dosage required for the MAO-B inhibition, or the psychedelic drugs and other recreational drugs affected by th p-glycoprotein.

-josef



Yea, that information is hard to find. If someone knows, please post about.


Some visuals were present too! They were the most colorfull visuals I have had :D but they just seemed to last a fraction of second.They where pretty different from the ones you get with DXM or LSD. They were more like something you think you saw... like the zolpidem or amanita ones but not vibrating and transparent. They were colorful, matt and it feels like they were flowing althought you dont see that.

-josef



This is all from black pepper? No other herbs combined with it?


Maybe is a sort of weird interaction with the 400mg of St John's Wort I take every day... I dont know ¿?
Someone has a clue ?
PS: sorry for the English :P

-josef



Don’t worry about language. No one really cares about that here. As long as the meaning gets across that’s all that matters to me.


It might be the Wort doing something. But I get effects from black pepper alone that feel similar to a melatonin build up. For me is lasts about 3 hours and fades away. Some people get mild visual effects from melatonin, I don’t, but some people do. Maybe you’re experiencing a prolonged melatonin boost?

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69ron

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#23 [url]

Jul 1 08 5:05 AM

I tried extracting piperine once. What a mess. It made everything smell like pepper. I'll never do that again!

I would like to try playing around with pure piperine a little more in the future. Next time I’ll just buy it already in pill form. I’m sure there are a lot of good uses for it. It messes up the effects of elemicin, but may have very beneficial effects for myristicin and safrole.

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#24 [url]

Jul 3 08 7:24 AM

Ron: It only was common black pepper that was lying around in the kitchen.
I usually take the 400 mg cap of st john's wort around 8 in the morning. I take only one because I`ve found that the 3X300mg dose makes me feel ill. Even the 2x300mg makes me fell bad some days, so the best tolerated dose was 400mg in the morning. (maybe im a litlle too sensitive with this herb)
--
Based on my experience, I dont think it was a melatonin boost. I've tried melatonin before at different doses and timings (compared to the sleep time) trying to get lucid with it. It gets my sleepy a while, but after the sleepyness has gone it's pretty difficult to sleep :P Nothing visual nor enjoyable.
Also, the dreams are disturbing and can`t be controlled no matter if you are lucid or not (that's only my case... usually the melatonin dreams of other people are calm and esailly controled). Also, the way melatonin works (in lucid dreaming context as far as I know) is being a serotonergic that supressees REM sleep, so when the effects wears out, you get pretty vivid and long REM rebound.
Anyways... it didn't felt like melatonin... but It's deffinitelly something related to the sleeping process.
Maybe what I felt was a sort of prolongation of the hypnopompic state and the visuals I saw where actually remaining dream-visions that can be seen after the dream!!!
Now I think about it, that's the best way I can describe the sensation! I just have to add that the dream itself was pretty trippy and full of colors. :D

However , still no idea of the causes of this phenomena.
--
Abbout timing:
That day I think I took the pepper at 5:00 pm, and slept about 2 hours.

I havent got much time to experimetn more with it.
All I can say is this: When I take it and remain awake, I just get a little hapy and willing to do things (I mean... it`s like I want to do things, not that I am stimullated).

Another day I took some before going to sleep, and in the next morning I didn't experienced nothing at all... I didn't have time to remember my dreams that day so I don't know if they were affected.

Another day, the nap was about 4 hours :D and I didnt noticed nothing but a remaining happy feeling.
 
So, as you said, Ron, I think the effects dosn't last more than 4 hours

As soon as i have time to take naps, I will test some more and post the results. :D (I' ll also make some tests with metylene blue... last day I think something happened with it, but I'm not sure. This test will take more time :S)
--

, I've read that the way pipperin increases bioavailability of curcumin and Q10 is by inhibiting the p-glycoprotein.

As far as i understand, this is possible because the p-glycoprotein helps to get rid of the xenobiotics, by enhancing the absortion into the liver hence causing a more extensive first pass metabolism (i've also read that this phenomena in fact helps MAOI's leading them to the MAO's and therefore inactivating them).
P-glycoprotein also seems to recognise xenobiotics that have reached the brain and get them out the BBB. I saw a link that proved that quinine (or quinidine... not sure) inhibited t P´glycoprotein and this allowed loperamide to cause CNS effects causing respiratory depression.
Sadly, as I read in bluelight, it doesen't seem to haveany recreational effects (or at least in the "normal" doses of loperamide), but it helped with some kind of opiate withdrawal or something like that.

However, this kind of transport is new to me, so maybe all Im telling you is wrong AND stupid XD.
Here is a link i've found recently that explains it a little and have a list of the p glycoprotein inhibitors, inducers and substrates.
http://www.genemedrx.com/PGP_Introduction.php


I think this p-glycoprotein inhibition has a lot to give to the drug users and pepper may become a great ally... I will research more.
--

Something I`ve noticed is that st johns wort is an inducer of p.glycoproteine and CYP3A ; and pipperine is an inhibitor of both of them...
This interaction can explain the reaction in any ways??


Peace

"The greatest thing You'll ever learn Is just to love And be loved In return" Sorry if mi posts feel harsh or rude. It's my bad level in English :P

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#25 [url]

Jul 3 08 9:52 AM

 Great find , Josef ! Piperine interactions seem indeed lead to a broad investigation of drugs metabolism beyond the CYPs analysis.
So, the safety to inhibit p-glycoprotein is another aspect to take into account. 


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toastus

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#26 [url]

Jul 3 08 3:13 PM

If piperine inhibits something that prevents xenobiotics from crossing the BBB, shouldn't that be EXTREMELY useful in activating MANY things that won't cross the BBB?

Keep in mind that it could be EXTREMELY dangerous, and that system is definitely there for our protection, but...

Imagine if you could deactivate the systems that prevent mescaline from crossing the BBB. You could feel the effects of the actual mescaline molecule, instead of its metabolite. At first glance though it looks like Piperine doesn't inhibit something that prevents many of our useful things from entering the brain, right?

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69ron

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#27 [url]

Jul 3 08 5:39 PM

Piperine really weakens elemicin so I avoid eating black pepper if I'm going to use elemicin.

When taken on it's own, I get a "melatonin effect" from piperine which I don't like. Piperine is present in small amounts in a lot of herbal pills. It's often claimed to help you absorb things better. It's used as a universal potentiator and is found in all kinds of supplements. I'm not too sure just how effective it is in a lot of cases. I think it's overused in general. But it's very effective for helping to activate curcumin. This is proven. How it works is still somewhat debated.

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#28 [url]

Jul 8 08 12:06 AM

I haven´t benn able to find any usefull info about the p-glycoprotein. If someone finds out anything please post it. I would be exttemelly glad :D

"The greatest thing You'll ever learn Is just to love And be loved In return" Sorry if mi posts feel harsh or rude. It's my bad level in English :P

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69ron

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#29 [url]

Sep 20 08 8:18 PM

Earlier in this thread I mentioned that black pepper mostly inhibits CYP1A2. After doing extensive research, I found that the source that stated black pepper was primarily a CYP1A2 inhibitor was probably not correct. Most sources don’t say black pepper is a strong CYP1A2 inhibitor.

Most sources state that black pepper is a strong inhibitor of CYP2C9, CYP2D6, and CYP3A4, with only minor effects on CYP1A2.

Some sources say black pepper induces CYP2D6 without giving references to any studies supporting this claim. It is highly doubtful that black pepper induces CYP2D6 because black pepper greatly weakens the effects of elemicin, which is an effect shared by all potent CYP2D6 inhibitors.

One problem with enzyme inhibition studies is that many of them give conflicting information. There are several reasons for this. Some enzymes take longer to inhibit than others, and so testing for inhibition too early can give inaccurate results. At the other end, some enzymes recover from inhibition very rapidly, so testing for inhibition to late might give inaccurate results. A good test will measure enzyme inhibition once every 15 minutes or so for several hours straight, and repeat the test with various dosage levels to give more accurate results. Unfortunately, such tests are rarely done.

Some compounds both inhibit and induce the same enzyme. For example, caffeine inhibits CYP1A2, but it also induces it. Unfortunately, the information about when it inhibits it and when it induces it is hard to find. It’s very likely that caffeine induces CYP1A2 at a different time interval than it inhibits it.

This kind of interaction can mess up enzyme inhibition test results. For example, it might take 2 hours to fully inhibit CYP1A2, but if tested only after 15 minutes, the inhibition test might say it’s a weak inhibitor of CYP1A2 or an inducer. Also some compounds only inhibit an enzyme strongly at certain doses, and might actually induce it at another. Caffeine is said to both inhibit CYP1A2 and induce it. It obviously doesn’t do both at the same time with the same dose. It probably inhibits it at one dosage, and induces it at another, or inhibits it first, then induces it later, or visa versa. But I can’t find any studies that show these details. There’s inadequate research.

One thing that I’ve recently noticed is that drinking coffee during the effects of elemicin is always better than using elemicin after drinking coffee. Because caffeine both inhibits CYP1A2 and induces it, it’s hard to know which of these actions is making elemicin more potent if you drink coffee during the effects of elemicin, and which is responsible for the weaker effects if you drink coffee before taking elemicin.

Because CYP1A2 inhibitors are generally good to use with elemicin (such as German chamomile, cayenne pepper, etc.), and drinking coffee during the effects of elemicin works better than drinking coffee prior to using elemicin, it’s my belief that caffeine probably inhibits CYP1A2 for a short time period, and then it induces CYP1A2 for several hours later.

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#30 [url]

Nov 1 08 7:18 PM

   
...
One thing that I’ve recently noticed is that drinking coffee during the effects of elemicin is always better than using elemicin after drinking coffee. Because caffeine both inhibits CYP1A2 and induces it, it’s hard to know which of these actions is making elemicin more potent if you drink coffee during the effects of elemicin, and which is responsible for the weaker effects if you drink coffee before taking elemicin.

-69ron

Let's not forget that coffee is much more than caffeine. It's a pretty complex soup of phenols, essential oils, bad stuff like acrylamide, etc. 69ron, do you get the same effect from ingesting pure caffeine with elemicin that you get from coffee?  Have you tried this?

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69ron

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#31 [url]

Nov 1 08 11:42 PM

Treppenwitz, I haven’t used pure caffeine with these oils enough to say much about it. I prefer the effects of coffee over pure caffeine, because of the other compounds it contains. So I rarely use pure caffeine.

At some point I should do some tests using just caffeine to see if the caffeine is causing the potentiation or not.

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sativa

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#32 [url]

Feb 9 09 9:42 PM

Piperine as an MAOI

A total of seventeen phytochemicals including seven alkaloids (piperine, strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine), four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial. Among these compounds, piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine on MAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the K(i) and K(I) were determined to be 35.8 and 25.7microM, respectively. For paeonol, the K(i) was estimated to be 51.1 microM. The inhibition of piperine and paeonol on MAO B was of competitive type with K(i) values of 79.9 and 38.2 microM, respectively. The inhibition of emodin on MAO B was of mixed type with the K(i) and K(I) data of 15.1 and 22.9 microM, respectively. The present investigation showed that the phytochemicals piperine, paeonol and emodin are potent MAO inhibitors whereas other compounds were inactive against any type of MAO at 100 microM in the present assay.

-http://www.erowid.org/references/refs_view.php?ID=7535

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69ron

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#33 [url]

Feb 12 09 6:52 AM

Rutin is a much stornger MAO-B inhibitor with an IC50 value of 4 microM. Apidenin's IC50 for MAO-B is 6.5. Quercetin's is 11 microM. Piperine is pretty weak.

As for MAO-A, quercetin's IC50 is about 2.8 microM, apigenin's is about 1 microM, harmaline's is 0.0045 microM!

So piperine is not of much use as an MAOI. These other easy to get compounds are many times stronger.

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#34 [url]

Feb 20 09 1:32 PM

What's the standart dose of piperine to boost curcuma oil extract ?

-romanesco

I've been reading about Black pepper with Turmeric as an MAOI.  At low doses it inhibits MAO A and higher doses it does A and B. 

It sounds like 5 teaspoons of turmeric and 1 tsp. of black pepper at the same time is supposed to be enough for decent MAOI inhibition for a about 4 hours.  Most reports said people were taking it in milk or capsules.   IDK if the oil has all the goodies you want...

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sativa

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#35 [url]

Jun 8 09 5:04 AM


Piperine, a piperidine alkaloid from Piper nigrum re-sensitizes P-gp, MRP1 and BCRP dependent multidrug resistant cancer cells.

Source

College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China.

Abstract

Over-expression of P-gp, MRP1 and BCRP in tumor cells is one of the important mechanisms leading to multidrug resistance (MDR), which impairs the efficacy of chemotherapy. P-gp, MRP1 and BCRP are ABC (ATP-Binding Cassette) transporters, which can expel a variety of lipophilic anti-cancer drugs and protect tumor cells. During a screening of MDR reversal agents among alkaloids of various structural types, a piperidine alkaloid, piperine (a main piperidine alkaloid in Piper nigurm) was identified as an inhibitor. Piperine can potentiate the cytotoxicity of anti-cancer drugs in resistant sublines, such as MCF-7/DOX and A-549/DDP, which were derived from MCF-7 and A-549 cell lines. At a concentration of 50 μM piperine could reverse the resistance to doxorubicin 32.16 and 14.14 folds, respectively. It also re-sensitized cells to mitoxantrone 6.98 folds. In addition, long-term treatment of cells by piperine inhibits transcription of the corresponding ABC transporter genes. These results suggest that piperine can reverse MDR by multiple mechanisms and it may be a promising lead compound for future studies.

-http://www.ncbi.nlm.nih.gov/pubmed/21802927


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#36 [url]

Aug 8 09 7:20 AM

So then would this be useful for someone trying to treat cancer holistically? Could it perhaps re-sensitize cancer cells to herbal treatments? Can someone explain this?

"Life lived in the absence of the psychedelic experience that primordial shamanism is based on is life trivialized, life denied, life enslaved to the ego." herbs.maxforum.org Kambo.tk

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#39 [url]

Mar 22 13 4:15 PM

diet matters

not to mention body chemistry. when these tests are being performed there should be a very detailed bioassay and diet monitoring. what kind of caffeine is being used?. how much? with what?

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#40 [url]

Mar 22 13 4:25 PM

@sativa

good report on dmt nexus about your piperine extraction. Does seem fairly easy and forgiving.

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