This document was written by William White, author of the DXM FAQ. This
is the text version of the document.
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Bioavailability Enhancement with Solvent Technology
Abstract
Pure dextromethorphan hydrobromide (DXM HBr) has become available for
research use within the past few years. However, many amateur researchers
investigating this compound have had considerable trouble due to the low
bioavailability of DXM HBr in its native state. This document outlines a
method for increasing bioavailability using easily available phase-transfer
agents.
I. Introduction
Prior to 1996(ish), DXM HBr was only available to most amateur researchers
in commercial preparations (Robitussin, Vicks, Drixoral, etc.), which
contain disagreeable quantities of inactive ingredients; many preparations
have other active ingredients which make them unsuitable for use within the
research context. With the notable exception of Drixoral Cough Liquid Caps
(which are no longer marketed), few preparations are ideal for research at
entheogenic doses.
Recently, several companies have begun reselling pharmaceutical grade DXM
HBr to researchers who wish to work with this compound. At first this
seemed like the perfect solution to the problems with DXM bioassays
outlined above. However, it soon became apparent that DXM HBr in its native
form is unpredictably absorbed in the stomach, which can lead to numerous
problems including but not limited to:
* slow absorption in the GI tract, reducing the "peak" and increasing
the DXM/DXO ratio, with subsequent enhanced activity at sigma
receptors and dysphoria
* delayed onset time, leading some people to redose prematurely (and
overdose)
* prolonged periods of intoxication and hangovers
* potentially increased risk of neurotoxicity
Obviously, all responsible researchers wish to minimize the risks to their
lab animals, and so a better solution was designed.
Early moral of this story: sometimes you have to take one step back to take
two steps forward. We'll "step back" to using OTC products, and step
forward to a solution applicable to research use.
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II. Theory
The low bioavailability of DXM HBr is a direct consequence of its
exceedingly low solubility in polar solvents (i.e., the water in your
tummy). On the other hand, DXM dissolves quite well in ethanol, but once
the ethanol reaches the stomach, it tends to be diluted by the existing
liquid there (field tests with DXM HBr in EtOH solution show it crashes out
rather spectacularly as dH2O is added bringing the conc. of EtOH below
about 15%; in the ion-rich environment of the average primate stomach this
is probably much worse).
For reasons that are beyond me but nonetheless seem fairly obvious, once
the DXM HBr comes out of solution it tends not to be absorbed, and probably
rides along with the rest of the stomach contents until reaching the basic
environment of the intestines. At this point, the DXM will be absorbed, but
very, very slowly, as it makes its way through the meandering plumbing of
the upper GI tract.
This is not good. Why? Four reasons. First, it flattens the peak and
increases the duration of the experience (just as with any other drug
absorbed slowly). Second, it might increase the DXM/DXO ratio due to enzyme
competition, and most lab primates seem to prefer lower DXM/DXO ratios.
Third, NMDA receptors are funny critters, exhibiting rather startling
tachyphylaxis, and basically, if you don't nail `em quick, you lose a lot
of potential effectiveness. Fourth, some of it may not absorb at all,
putting the entire experiment at risk of becoming a WOMBAT (Waste Of Money,
Brains, And Time).
So, the desire is to increase the absorption rate of DXM HBr into the
bloodstream, hopefully doing all of this work in the tummy before the
chemistry changes and your lab primate spends the next 12 hours at a +1/2
wondering if s/he should take more.
The good news is, there's no need to reinvent the wheel here. Instead,
we're going to use the existing PEG in a single dose of over-the-counter
liquid gelcaps to dissolve a much larger quantity of DXM.
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III. Phase-Transfer Agents
Normally, polar and nonpolar materials cohabitate about as well as
Massachusetts bleeding-heart liberals and white separatists at a shotgun
wedding. However, there are ways around this problem. You've probably
encountered several, actually, including:
* soap (that's what it's for, after all)
* eggs (mix oil and water and get mayo)
* quaternary ammonium salts (well, maybe you haven't seen those)
None of the above are particularly appetizing, however (well, OK, I like
eggs, but the idea of DXM eggnog turns my stomach). Modern science however
has given us some nifty chemicals which do the same thing, notably
including: polyethylene glycol
Yup, that's right, polyethylene glycol (PEG), a polymer made up of
antifreeze (don't worry, it's perfectly safe, even though the monomer --
ethylene glycol -- is not). This nifty little critter lets the hydrophobic
DXM molecule careen around inside the polar environment of the tummy until
it sneaks into the bloodstream.
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III. Implementation
So where do you get PEG? Well, you can probably buy it from a chem
supplier, and there's more than likely an over-the-counter source for pure
PEG somewhere, but damned if I could find it. Instead, I found: Liquid
Capsules. See Section IV below for specifics.
Now, I know what you're thinking: "but they took the Drix off the market!"
Yes, they did, but I'm about to teach you how to make your own damn Drix,
and you'll only need two pills. You will need the following; sources listed
in [brackets].
* DXM HBr powder [check online for current suppliers]
* An *accurate* scale [http://www.balances.com/]
* A fabric pin, thumbtack, etc. [look under the couch cushions]
* A package of Liquid Capsules containing polyethylene glycol. See notes
below (IV. Selecting a PEG Source) [drugstore]
* A small quantity of vodka, 80 proof is fine [liquor store]
* A small shotglass or similar small vessel [liquor store]
* A swizzle stick or other stirring device (don't use a straw or coffee
stirrer, you'll lose product) [grocery store]
* A lab primate for bioassay testing. Your lab monkey should be
reasonably well-behaved (if not, you can always spank him), in good
health, etc. Feeding the lab critter at least two hours prior to
testing is recommended; otherwise, food in its stomach might interfere
with this experiment. [you're on your own here!]
and, if your monkey is squeamish about bad-tasting things:
* an irrigation syringe, the kind used to clean out the mouth after oral
surgery [drugstore]
* size 00 capsules [drugstore, GNC, hippy grocery store, vitamin store]
Instructions:
1. Measure out the desired quantity of DXM HBr for the experiment, but if
your Liquid Capsules contain DXM be sure to subtract it (e.g., if you
are using Liquid Caps containing 30mg DXM in two caps, and you want
360mg of DXM, measure out 330mg). Place the DXM into the shotglass.
2. Take a "normal dose" of Liquid Capsules (usually two caps) out of the
package. Take one capsule, and pierce each end with the pin (or
thumbnail, or whatever). The liquid will remain inside due to the
surface tension. Hold the capsule over the shotglass. Place your index
finger over the top hole, and squeeze the capsule with your other
hand, causing liquid to drizzle out onto the DXM HBr powder. Release
your finger over the top hole, and then relax to let the capsule
regain its shape. Repeat, milking the liquid out of the Liquid Capsule
until it's all in the shotglass. Repeat for the other Liquid Capsule.
3. If your quantity of DXM exceeds 600mg, you might want to repeat with a
second dose (another two caps). DO NOT GO ABOVE TWO DOSES!
4. With the swizzle stick, or other convenient stirring implement, stir
slowly until the DXM is completely dissolved in the goo from the
Liquid Capsules. If it doesn't become completely transparent (it may
take a few minutes of stirring), don't worry too much.
5. Add a *small* amount (15ml or so) of alcohol (Vodka) and stir for
about 1 minute until smooth.
Congratulations, you're done. Now, you have two options: give it to your
lab monkey as-is, or put it in capsules. So, either:
* Add more alcohol to the shotglass until about 2/3 full and stir
briefly. Give to your lab monkey to shoot and chase with water (salt
and lemon wedge optional).
or
* Suck the material in the shotglass into the irrigation syringe, and
then fill empty size 00 capsules with the syringe. Close the capsules
and feed to your lab monkey.
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IV. Finding a PEG Source
This is rather simple.
Go to your nearest drugstore, convenience store, grocery store, etc., and
find the cold and cough medicine aisle. Now, start looking for "softgels",
"liqui-caps", "liquid caps", or whatever they're calling them these days --
basically, soft pliable gelatine capsules with liquid inside. See the side
of the box for the inactive ingredients, and look for any of the following
three:
1. Polyethylene glycol
2. Povidone (polyvinylpyrrholidone)
3. Propylene glycol
in that order of importance. If you can find one that has all three, great.
If not, make sure to get something that at *least* has PEG (polyethylene
glycol). Why povidone matters is, like many things, beyond me, but it seems
to make a difference (povidone is a synthetic polymer that creates a
hydrogel; it passes through the gut unchanged, but I suspect it may help
solvation).
Robitussin [tm] makes several brands that will work, e.g., Robitussin Cold
& Cough [tm].
Remember, your lab animal will only be taking *one or two doses* of
whatever you pick, so it doesn't really matter what active ingredients are
in it, so long as they aren't otherwise a health risk to the lab critter.
However, just on general principle, try to avoid acetaminophen.
Now, if you happen to run across two different liquid gelcap products which
have completely different types of drugs (e.g., product A has an
antihistamine and analgesic, product B has a decongestant and cough
suppresant), then you can, of course, use both at the same time, increasing
the amount of PEG used (more PEG means faster absorption).
Remember: AT NO POINT should you give your lab monkey more than two doses
of ANY over-the-counter drug! More than two doses will probably affect the
lab animal's perception of the DXM effects, and more than four or five may
be dangerous, depending on the drug and its class (acetaminophen, for
example, tends to have a low safety margin).