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bioperine,bioavailability,pre/postloading,mdma

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beta theory

Bluelighter
Joined
Oct 9, 2004
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Bioperine: A Patented Phytonutrient to Enhance the Bioavailability of
Nutritional Supplements

Bioavailability: The degree to which or rate at which a drug or other substance is absorbed or becomes available at the site of physiological activity after administration

I have recently heard about this substance bioperine. I think that it could definately be very useful in everyone's pre/post loading regemin, allowing you to get the most absorbtion from your vitamins and antioxidants See Here. I don't know much and was hoping some of the BL'ers were familiar with this substance. How exactly does it make the nutrients .etc. more bioavailable. Further more, will this substance only increase the bioavailability of nutrients, or would it work on something like mdma as well? What are its restrictions in this action?

peace,
beta theory
 
Haven't heard of this stuff, but as a general rule the majority of 'health food'/supplement products are junk science or close to it. The 'health food' industry scored a legislative coup in America in the 80s, and since then have been virtually unregulated. Take any claims by the supplement people with a few metric tons of salt.
 
Bioperine aka piperine containing extract. Piperine is a broad spectrum cytochrome P 450 inhibitor and a P-glycoprotein inhibitor...

Mixing inhibitors with MDMA is a bad idea, = unpredictable results... though all the opioid users in other drugs might think it is fun...
 
BilZ0r said:
Bioperine aka piperine containing extract. Piperine is a broad spectrum cytochrome P 450 inhibitor and a P-glycoprotein inhibitor...
Click to expand...

resulting in the "increase of bioavailability" effect. I wonder how long the inhibition lasts. It seems like a valid tool for getting the most out of a vitamin regemin, though nothing more.

peace,
beta theory
 
Well... maybe... I wouldn't bother personally... Most of the water soluble vitamines have specific uptake pathways,
 
Just out of curiousity, why is it dangerous to inhibit the CYP's when using mdma. Aren't people with CYP2D6 deficiancy ok to take mdma?
 
Because it leads to unpredictability. Because now, not only are you dealing just dealing with the normal unpredictability of the pharmacokinetics of MDMA, you've got to factor in the unpredictability of how effected the enzyme was.

Well if someone was hoenst to god CYP2D6 deficent, then it would be cause for concern.
 
They have a deficiency but it is on the order of tens of percent; they aren't completely lacking the CYP2D6 enzyme.

A lot of the problem is first-pass metabolism, which many people try to circumvent by plugging etc. Get rid of CYP2D6 and you'll get rid of that. but if you do that you can get abnormally high plama levels of the drug. MDMA's effect is non-linear for that reason; taking two pills is way more than double the effect of taking one.

The anti-HIV drug retonavir, for instance, blocks a lot of CYP enzymes. People have died combining it and MDMA.
 
VelocideX said:
They have a deficiency but it is on the order of tens of percent; they aren't completely lacking the CYP2D6 enzyme.
Click to expand...

I didn't realize it was such a small percent. I guess as BilZ0r said, if they were 'truely' deficiant, it would be a concern.

I just don't get how method of ingestion can make a difference in anything except 'come up' time. And maybe how 'hard' it hits you. I am starting to believe that duration is directly linked to to down regulation with little regard for anything else.
 
First-pass metabolism plays a huge role in determining the peak plasma concentration. Go look up the study of a person who was taking retonavir who died subsequent to MDMA ingestion. I believe that his plasma levels were 5x what would have otherwise been expected.
 
Yeah, people always make the odd assumption that taking inhibitors, or dosing in different ways, can't effect plasma peak concentration, just the time your high for.

Think about IV usage. If you IV the same amount as oral, you're gonna get a high plasma peak right? Everything else is just on a continuum from there...

And, if there is no first pass metabolism (or weird metabolism), and no tissue deposition, if you plot a graph of time verses plasma concentration, the area under the curve (AUC) should be equal between the oral and the IV dose.
 
You always see people posting about how taking ecstacy depletes your serotonin. I guess it would be unfair to claim the receptor downregulation is solely to blame, but surely the MAO is not breaking down this much serotonin. Is there any other way for serotonin to be diminished? Seems that the neuron is plenty capable of sucking the serotonin back into itself via uptake. Basically there is no way to extend the performance of mdma short of increasing the amount of activity receptors can stand. Would it be correct to say, its not how much you take, it's how much you (your receptors) can take?

peace,
beta theory
 
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If MAO was broken down, then repeated usage of MDMA would get you higher.
 
Bugger I posted a message but it seems to have been lost.

Think about how MDMA works. It has a half-life of 9 hours, so even after the high is gone there's still significant reuptake transporter blockade. MDMA partially inactivates tryptophan hydroxylase, so a neuron's production capacity is effectively lowered.

With the ability to "vacuum up" extracellular 5-HT impeded, and the ability to produce serotonin "de novo" impeded, its no wonder that depletion occurs.

You have to remember that MAO is found both within and outside of the cell body; some synaptic 5-HTP is broken down by extracellular MAO.
 
Ahh, but the half life is very stereoisomer selective... I forget which one is still floating around, but they have different affinities for the transporters... I've posted on this before I'm sure...

Are you sure MAO is found synpatically?
 
I always thought it was? I swear I'd seen something on it.

If it wasn't, does that mean that extracellular monoamines would just dissipate? They've gotta go somewhere.... e.g people on SSRIs.
 
VelocideX said:
Think about how MDMA works. It has a half-life of 9 hours, so even after the high is gone there's still significant reuptake transporter blockade.
Click to expand...

I didn't know that the reuptake transporters were blocked from mdma usage. I thought this was the whole reason for the possiblity of neurotoxicity. Dopamine getting sucked up throught the reuptake transporter and broken down by the MAO. Also, does mdma cause the reuptake transporters to work backwords or is that study still in the works?


peace,
beta theory
 
It's fairly well agreed that amphetamines cause the reversal of the relevant monoamine transporter.

Even after the high is gone, the transporters still take the MDMA molecule up into the neuron. Serotonin release is still caused, albeit not as effectively. During the time that MDMA is being taken up this constitutes an effective blocking of the transporter.

The dopamine theory fell into disfavour some time ago.

In any event, even if the transporter can't latch onto a serotonin molecule inside to transport out, I suspect that this still prevents the transporter from bringing extracellular serotonin into the neuron for a period. Bilz0r?
 
VelocideX said:
The dopamine theory fell into disfavour some time ago.
Click to expand...
What is currently the suspected culprit of neurotoxicity?

Also, when mdma is taken up through the transporter and seratonin is taken out through the transporter, what hinders the transporter from taking the serotonin right back up?

peace,
beta theory
 
In any event, even if the transporter can't latch onto a serotonin molecule inside to transport out, I suspect that this still prevents the transporter from bringing extracellular serotonin into the neuron for a period. Bilz0r?
Click to expand...
I'm not sure... I can see why you'd think that, but I actaully don't -think- it is the case... amphetamine-induced release, isn't just uptake reversed... I -THINK- that the transporter still has its extracellular face, facing outwards when its outwards transporting (i.e. amphetamine is acting)... so I think its efficacy is largely uneffected... only when it is actaully outward transporting will it not be able to take up the monoamine...

What is currently the suspected culprit of neurotoxicity?
Click to expand...
People have gotten hot on a neurotoxic metabolite again, citing the fact (which I don't think is a fact), that direct application of MDMA to the brain is not neurotoxic.

Also, when mdma is taken up through the transporter and seratonin is taken out through the transporter, what hinders the transporter from taking the serotonin right back up?
Click to expand...

Nothing.
 
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