How to potentiate your stimulants...

[skydigger]

Reading contradictory statements in my aunts PDR left me a little bit confused. Yesterday with a little luck I got things figured out.
The statements were in two different sections of the book stating facts on Amphetamine.
The first said that

Acidifying agents (grapefruit juice) can potentiate the effects of amphetamine. The second stated that

basifying agents will slow excretion of amphetamines, therefor increasing the amount of the drug that passes into the bloodstream.
This confused me because grapefruit juice is acidic and it will obviously acidify your stomach. Whereas baking soda (and other basifying agents) will obviously basify your stomach. So how is it possible that both statements are true?
After digging around (I'm pretty sure it was another site) someone mention something called Naringin.

WHAT DOES IT DO?
Naringin is an aldose reductase inhibitor.
CAUTIONS
See the Disclaimer.
Naringin is thought to be the component of grapefruit that interferes with the cytochrome P450 pathway in the liver. This pathway is the primary Phase I detoxifier in the liver. (See detoxification in The Basics of Health.) It has been recently discovered that grapefruit changes the dose of many kinds of drugs by affecting their metabolism. Before taking this product ask your pharmacist if any of the prescription or other drugs you take are affected by grapefruit. If so, do not use this product.
I've read lots of unsubstatiated claims and myths about orange juice and grapefruit juice here and elsewhere, but I haven't read about Naringin so I thought I would share it and would welcome any comments if anybody has any experience with it.
The amount of grapefruit juice that you have to drink in order to have enoungh naringin may well be a bit much, so for our convienience it is available in pill form.
I take prescription dexedrine, and I'm going to search around the health food stores today and see if its available so I can give it a shot.
Here's a link to the page where I swiped the quote, and I'd suggest doing a search for Naringin to learn a little more about how it interacts with various meds.
I've seen warnings about grapefruit juice and dexdrine, so likely meth users (not that you need it) and with any luck you E-tards will get a little more kick out of your rolls.
The Narinase Page
[ 29 June 2002: Message edited by: skydigger ]

 

[quale]

Okay a little correction. Grapefruit juice seems to primarily inhibit the CYP450 3A4 pathway...this is the primary route of decomposition of some benzodiazapienes (i.e. xanax) but not the primary method of metabolism for the amphetamines. Moreover, I had heard, although I am not sure, that grapefruit juice only inhibits the action in the intestine (so it helps with oral absorbtion but if you are smoking/snorting not a big difference).
The amphetamines (meth, amphetamine, excstasy etc..) are primarily metabolized by CYP450 2D6. This is good news as practically everything in the world inhibits this pathway...a short list:
amiodarone
celecoxib
chlorpromazine
chlorpheniramine
cimetidine
clomipramine
cocaine
doxorubicin
fluoxetine
halofantrine
red-haloperidol
levomepromazine
metoclopramide
methadone
mibefradil
moclobemide
paroxetine
quinidine
ranitidine
ritonavir
sertraline
terbinafine
If you are trying to do this OTC remember that cimetidine is the active ingredient in tagament HB. This isn't a strong inhibitor...I think medically they use quinidine when they want something strong but I don't know where this is availible.
Ohh and be carefull with the cimetidine as I think it works primarily not by directly inhibiting the enzyme but by reducing hepatic blood flow, so it reduces the effectiveness of nearly all the CYP enzymes. Shouldn't really be an issue but don't take it and then try some dose of some bizarre ass drug without researching first.
Your second quote just doesn't make sense. Slowing absorbtion should not increase the amount that make it into the bloodstream...this is just weird...and also sounds backwards.
[ 29 June 2002: Message edited by: quale ]

 

[Dr_Bombay]

I can vouch for grapefruit juice potentiating the benzo group. Really kicks them in, don't know about the amps though. Hope this helps.
one,
bombay

 

[quale]

Just out of curiosity Dr_bombay which benzos? Was it xanax?
I haven't had much noticeable effect with 3A4 inhibitors and klonopin...I understood the longer lasting benzos were almost completly absorbed anyway...but then again I am pretty benzo resistant.
Also did it make them stronger or just hit you harder?

 

[skydigger]

Athough the quotes were not word for word, they DID come from my aunts PDR.
the first qoute is more or less accurate, the point of the second was that "basifying your stomach will slow the excretion of amphetamine allowing a higher concentration to be absorbed.
That can be confirmed at rxlist

 

[skydigger]

i did some searching around various sites to confirm what I had read.
Many sites listed benzos as well as a whole host of drugs that interact with grapefruit juice.
None mentioned amphetamine, but perhaps they're not telling us on purpose.
Anyway, here's a response from doctor when asked about citrus juices and ADD meds.

Grapefruit, however (pulp or juice) is a different critter from the other citrus fruits. The mild reduction in absorption that it causes is overwhelmed by another of its affects: grapefruit has a chemical in it that inhibits an enzyme in the human liver, an enzyme that metabolizes amphetamines. Physician dosing of amphetamines is based on the assumption that the patient has a normal rate of metabolism and removal of these drugs. If grapefruit has "poisoned" the enzyme, the body's concentration of amphetamine can rise to alarming levels, up to 10-13 times the normal level. This effect far outweighs any reduced absorption caused by the presence of the grapefruit acidity in the GI tract. And note that this effect is true whether or not the grapefruit is taken at the same time as the medication, so patients should not take grapefruit at all, at any time when they are on amphetamines. Remember, too, that grapefruit is in Sunny Delight, Fresca, and some other mixed-fruit beverages such as wine coolers. (This grapefruit effect can also enhance levels of several other frequently used meds, such as Procardia for blood pressure and Glucotrol for diabetes.) Again, Ritalin is not involved.
The general citrus effect is so minor that I don't mention it when prescribing amphetamines, but I do tell patients to avoid all grapefruit.

 

[quale]

Looking on rxlist seems to directly contradict your first quote from the PDR.

Acidifying agents - Gastrointestinal acidifying agents (guanethidine,reserpine, glutamic acid HCl,ascorbic acid, fruit juices, etc.) lower absorption of amphetamines.
Urinary acidifying agents -(ammonium chloride, sodium acid phosphate, etc.) Increase the concentration of the ionized species of the amphetamine.
Primary excretion - Both Groups of agents lower blood levels and efficacy of amphetamines.
Alkalinizing agents -Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.)increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentate the actions of amphetamines.
Taking agents which make your digestive system more basic should encourage the amphetamine salt to dissassociate more and be more fully absorbed.
I am really confused why it claims that Urinary alkalizing agents increase the concentration of the non-iodized version of the amphetamine. In either case it seems clear that bases potentiate and acids inhibit the effects.
Also all my research seems to suggest that grapefruit juice has no effect on the 2D6 pathway, the primary way amphetamines are metabolized. I think that doctor is just dumb or confused.
[ 30 June 2002: Message edited by: quale ]

 

[skydigger]

In either case it seems clear that bases potentiate and acids inhibit the effects.
It's clear, but it's not crystal clear.
Here's my quote from the ADD doc.

Grapefruit, however (pulp or juice) is a different critter from the other citrus fruits. The mild reduction in absorption that it causes is overwhelmed by another of its affects: grapefruit has a chemical in it that inhibits an enzyme in the human liver, an enzyme that metabolizes amphetamines
So, grapefruit is a special case. Even though its an acid, the compound (naringin) in the grapefruit overpowers the effects of the acid and it potentiates the amphetamine.
There are loads of websites discussing the drug interactions with grapefruit. As i said amphetamine wasn't listed on any, however caffiene and "various OTC allergy meds" are included. The original quote came from a nurses PDR.
Is it true? I don't know, I guess I'll have to try a little experiment.
[ 30 June 2002: Message edited by: skydigger ]

 

[Dr.groveller]

Originally posted by skydigger:

So, grapefruit is a special case. Even though its an acid, the enzyme (naringin) in the grapefruit overpowers the effects of the acid and it potentiates the amphetamine.

But, you haven't addressed Quale's response that it is a different pathway that grapefruit inhibits. Both statements (Quale, the ADD doc) cannot be true. Docs *can* be confused/flat out wrong.

The amphetamines (meth, amphetamine, excstasy etc..) are primarily metabolized by CYP450 2D6.
Can you cite a reference Quale? Grapefruit obviously interferes with an Enzyme. Either your doc has the wrong enzyme, or Quale does. As you said, no other site has referenced the potentiation of amphetamine due to grapefruit...
doc
[ 30 June 2002: Message edited by: Dr.groveller ]

 

[quale]

Some references. First just a table of CYP450 interactions. Note grapefruit juice is not listed as an inhibitor for the 2D6 pathway while this is the only route of metabolism shown for the various amphetamines (amphetamine MDMA).
CYP chart.
More references showing that grapefruit juice is listed as affecting the 3A and 1A pathway not 2D6:
grapefruit
Also this result is listed in the DXM faq (okay not a great reference but might as well throw it in).
Here is an abstract review article suggesting that grapefruit juices effects are primarily due to 3A inhibition in the gastrointestinal tract.
To back up my statement about it really only affecting oral absorbtion here is an abstract.
Ohh and here is another good reference suggesting that amphetamine CYP interactions are primarily 2D6 based.
[ 30 June 2002: Message edited by: quale ]

 

[Dr.groveller]

Originally posted by quale:
Some references.
Perfect, thanks!
doc

 

[fairnymph]

A couple things...
Despite inhibiting CYP 2D6, fluoxetine (i.e. Prozac) does NOT potentiate the effects of amphetamines and in fact slightly weakens the effects. My experience with some other drugs that inhibit CYP 2D6 demonstrate a similar pattern...
Urinary alkalinizers definitely potentiate amphetamines. I have observed this on a number of occasions.
Personally I haven't found grapefruit to do much, either with meth or MDMA...

 

[quale]

Yah but prozac does a bunch of other things too, such as interfere with uptake of amphetamines from various NT systems. Also I don't believe it is a strong inhibitor and presumably long term use builds a tolerance (i.e. after using prozac for a long enough time your CYP system starts produding more 2D6). Was this acute or chronic ingestion? If acute what kind of doses are we talking about (prozac is such a bitch because to get acute doses that reasemble the concentrations after say a week of taking it you have to take a shitload because of the long half-life).
I am wondering if you have tried other more potent/less side effect 2D6 inhibitors? Not that I am doubting the abscence of potentiation, despite the warnings alot of the CYP interactions seem to produce minimal subjective effects, but I am curious if they also lessened the effects/had no effect.
Also I am curious what alkalizing agent you used. I have never heard of half those urinary alkilizing agents and wouldn't even know where to begin finding them.
[ 30 June 2002: Message edited by: quale ]

 

[skydigger]

I did a little search myself and confirmed quales findings.
The Nurses PDR DID make the original claim though, unfortunatly they seem to be wrong.

 

[quale]

Well that is probably what got that online doctor all confused then. Unfortunately doctors tend to rely on these books (really can't be helped doctors have real jobs unlike me and can't be expected to spend all day browsing pubmed for papers) and sometimes they are horribly wrong.
The handbook of clinical (and something) pharmacology claims that oxycodone doesn't have that high of an abuse potential.
If we give our doctors crap for references is it any wonder they end up fucking up? No wonder I don't trust their prescription choices.

 

[yaesutom]

A couple weeks or so ago, I decided I was going to try taking a Tums with one of my 10mg Adderall's. But about 15-30 mins before that, i took 400mg of Cimetidine. I took the Adderall with the Tums, and I felt a very quick come up (usually Adderall has a slow, smooth come up for me), and i was WIRED for 2-3 hours. I felt like I had taken 4+ Adderall's, although it somehow felt different (maybe certain salts in the adderall were potentiated more than the others?). Then after 3-4 hours, i was completely down, and i felt nervous..anxious..irritated by people, and somewhat tired. Usually one 10mg Adderall will work longer than 3-4 hours (although a lot weaker in action).
So another day, i tried taking a couple capsules of baking soda with an Adderall...no potentiating effect noticed...
So i'm thinking it must have been (mainly) the Cimetidine? Why would the effects of the Adderall only last a STRONG 2-3 hours and then a fast come down/tiredness?
I will have to experiment more..

 

[NoriegA]

OK terrific. This doesn't have any real realation to this thread but my local pharmacy started putting lables on my xanix script that said not to drink or eat grape fruit juice while on this medication. I asked her why & she said the acidity would upset my stomach but I think she was lying...

 

[quale]

No noriega you are completly correct it is because grapefruit juice will help you get high with xanax .
yaesutom: Both the cimetidine and the tums will make your stomach more basic increasing both the speed with which the adderall hits you (especially releveant with adderall b/c as I remeber it is actually several differnt salts combined so as to dissassociate at differnt rates and affect you for longer) and the effective dose.
cimetidine seems to inhibit hepatic blood flow so it very well may reduce the rate at which the amphetamine is metabolized increasing duration. Of course it also no doubt help alkalinize your stomach. I am not sure how relevant the comedown is...if you are coming down from a large amount then feeling nervous anxious and tired are fairly normal while smaller amounts disappear without noticeable comedown. Could you *actually* sleep or just subjectively feel tired. Feeling tired but not being able to sleep is characteristic of stim comedowns for me.
Your baking soda experiment is really interesting, however, I tend to suspect their is a reason that capsules of baking soda aren't sold as antacids. Can't imagine why they wouldn't work well this way but it seems kinda strange.