ok, for those that asked - here is why mixing ephedrine with yohimbine is dangerous. (i am not saying i don't know people that have done this, btw).
and supersoldier, i am not aware of any OTC supp that combines Y and E. i am aware of some that used Yohimbe with NORephedrine. but not with ephedrine. totally different thang. NYC (Norephedrine/yohimbe/caffeine) is a GREAT stack
here is some info from Elzi Volk on why you shouldnot combine Y and E.
i have more info, but she explains it pretty well
Below written by Elzi Volk
beta-Adrenoceptors downregulate relatively quickly (depends on
dosage/time/administration). Consider that the density of skeletal muscle
beta-ARs decreases by 50% within 18 days in rats treated with clenbuterol (a
beta2-agonist) and by 40% as early as 3 days in rats treated with cimaterol
(again, in skeletal muscle). Rats infused (IV minipumps) with
isoproterenol, a beta-agonist, for 3 days reduced beta-AR density (~80%) in
adipocytes. Granted, these are animal models and not human, but human
studies of this type are scarce (given the compounds, dosages and tissue
samples required). We do know that beta-AR downregulation occurs in human
tissue as well with beta-agonists (there is lots of data with asthma meds).
The major side effect of beta-agonists is in the nervous system and cardiac
muscle. These beta-ARs downregulate as well, whcih reduces the "feel" that
you refer to. That is, you can tolerate a given dose more.
But remember that these agonists have an indirect effect as well. They
increase levels of catecholamines. These hormones also interact with the
alpha-ARs in addition to the beta-ARs. So there will be two regulatory
mechanisms acting on tissues: beta-ARs and alpha-ARs. Therefore, keep in
mind that ephedrine directly acts on the beta-ARs, but also indirectly acts
on the alpha-ARs (stimulates) via increased catacholamine concentrations.
Now remember that the effects of all these (both beta-AR-mediated and
alpha-AR mediated) are highly tissue specific. This pertains to cardiac,
blood vessels, skeletal, adipose, pancreatic, hepatic, etc. Getting
complicated, isn't it?
What I am trying to point out is that we need to look at the big picture
here (which is why I am so shitty at physics
. Effects of any AR agonist
or antagonist is going to depend on: density of specific ARs (both beta
subtypes and alpha subtypes) in a specific tissue, blood supply (which the
aforementioned will affect as both beta-ARs and alpha-ARs affect blood
supply), dosage and route of administration of compound, and duration of
administration of compound.
One (I won't discuss all of them here) of my hypotheses regarding the
continued fat loss seen with chronic ephedrine administration is that there
is increased tissue compartmentalization of the compound and its metabolites
with chronic dosing. In many of the studies with animal models, they use
very high dosages and they are infused IV. Oral administration has different
kinetics. And humans don't typically take the high dosages that they use in
animal models. So compartmentalization may take longer in humans.
Although I am not very knowledgble of pharmacokinetics (and Bill can
interject at any point here), microdialysis has shown that ephedrine (and
other compounds) does not appear in the extracellular space in adipose
tissue with acute administration. What induces lipolysis in these tissues
are the catecholamines, whose concentrations increase due to the
beta-agonists (and alpha2-antagonists). Although no studies specifically
support my contention, with chronic dosing these compounds may appear in the
adipose tissue and therefore have direct interaction with the adipocyte
beta-ARs. Some studies have shown the same with other adrenergic compounds.
For instance, yohimbine and its metabolites may take quite awhile to
compartmentalize in other tissues, as much of the research demonstrates
(which explains why it takes up to 4 weeks for any apparent effects of Y
treatment and penile erectile dysfunction).
Back to your question (yes, this is a bit of mental masturbation, but I've
been wanting to put this forth anyway). Is it safe to add Y when the side
effects of ephedrine wear off (which is an indicator that beta-ARs in
cardiac muscle are downregulated to an extent)? Just remember that Y has
it's own set of regulatory mechanisms. It blocks activity of the alpha2-ARs,
most notably on the neural terminals and on walls of blood vessels. This
results in increased concentrations of norepinephrine and vasodilation. So
its going to increase heart rate and BP. How this affects cardiac muscle
whose beta-ARs (at least, a good percentage of them) are downregulated, I'm
not sure (I avoid cardiac and kidney physiology). The vasodilation
properties would help maintain increased blood flow (stimulation of beta-ARs
induce vasodilation) in skeletal and adipose tissues, which in itself, would
help maintain lipolysis and increase clearance of NEFAs.
It would be logical from the standpoint of blood flow (you won't get any
direct effects of Y on fat cell alpha-ARs unless you chronically dose it)
that it would be helpful, but I question what it would do to cardiac tissue.
THAT alone is enough to make me hesitate. I've dosed yohimbine after
ephedrine (5 hours later) and thought I was going to have to call 911. I
like my ticker too much to take any chances. (and I already have a
pre-existing heart problem)
