An idea: Ephedrine and clonidine.

[JackiesBabyy]

Ephedrine works by releasing norepinephrine and, to a much lesser extent, dopamine. Taking a large dose (150mg for me) feels similar to amphetamine, giving mild euphoria and motivation, but also giving a lot of uncomfortable physical stimulation thanks to the large NE release.

In theory, couldn't taking a high dose of ephedrine with clonidine (a med that works by lowering the amount of NE in the brain) make ephedrine much more recreational? I can't find anything on google about anyone mixing them and the idea came to me when I read about clonidine.

 

[endotropic]

I guess the main concern would be the drop in blood pressure from the clonidine. I found one reference where the combo was used I.V. during surgery, but at much lower dosages than you're talking about:

Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence.
http://www.ncbi.nlm.nih.gov/pubmed/16731324

They say that the ephedrine doesn't counteract the hypotension from the clonidine at these doses, but really orally and at higher doses who knows.

 

[JackiesBabyy]

I guess the main concern would be the drop in blood pressure from the clonidine. I found one reference where the combo was used I.V. during surgery, but at much lower dosages than you're talking about:

Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence.
http://www.ncbi.nlm.nih.gov/pubmed/16731324

They say that the ephedrine doesn't counteract the hypotension from the clonidine at these doses, but really orally and at higher doses who knows.

That's odd - One of the most common side effects of ephedrine is hypertension, unless in that example a really low dose of ephedrine was used, OR if clonidine is an incredibly powerful antihypertensive.

 

[sekio]

clonidine is an incredibly powerful antihypertensive.

It's one of the strongest, not many other drugs can produce massive changes in physilolgy at 200 microgram doses.
Ephedrine is really limited in its recreational potential from what you've noted - the adrenergic side f/x. Therse are imparted from the beta hydroxy group.

 

[JackiesBabyy]

It's one of the strongest, not many other drugs can produce massive changes in physilolgy at 200 microgram doses.
Ephedrine is really limited in its recreational potential from what you've noted - the adrenergic side f/x. Therse are imparted from the beta hydroxy group.

Yes, but wouldn't a low dose of clonidine's ability to lower NE and thus adrenic side effects boost it's recreational potential? Or does ephedrine release NE in one area of the brain while clonidine lowers it in another?

 

[sekio]

Clonidine doesn't lower the release/concentrations of norepinephrine directly, it simply blocks norepinephrine and adrenaline from acting at your receptors.

 

[thegreatgeno]

Clonidine doesn't lower the release/concentrations of norepinephrine directly, it simply blocks norepinephrine and adrenaline from acting at your receptors.

Ah, so what would become of all the excess NE released by the ephedrine? Also, Clonidine is an a2 adrenic agonist. Aren't the types of drugs that block receptors antagonists?

 

[PoppyLlama]

to behonest, neither of these chemicals are good for recreation to begin with, and i doubt they're going to be very recreational when combined, they'll probably just be more dangerous and the same miniscule amount of pleasure (if any). you're just taking two drugs, neither of which are recreational, and on top of that they both counteract each other in their main effects.so what the hell is the point? lol

if you have to do drugs to have fun why not do some drugs that are ACTUALLY fun...i mean get some valium and a little coke, or some opiates and a little coke...or even some opiates and a little amphetamine or methylphenidate would be better than ephedrine and clonidine HA, what a joke. seriously, that sounds fucking awful.

 

[sekio]

Whoops, I got that almost entirely wrong.

Clonidine binds to the a2a adrenergic receptor, which is used by your body to "sense" the levels of norepinephrine/adrenaline. So when you take a dose your body then thinks "whoa man I'm producing wayy too much noradrenaline" and hence the natural release of NE falls.

The end effect is pretty similar to an almost complete blockade of the effects of your body's natural NE/Adrenaline release.

The problem however is that clonidine etc, in long term therapy,are liable to cause rebound effects like absurdly high blood pressures when therapy is discontinues.

I don't think ephedrine would really benefit from anything more than a very small dose of clonidine - it's got too much intrinisc activity at the adrenergic receptors anyway. (Not only does it increase release of NE/DA it also mimics the effects of adrenaline and norepinephrine)

 

[JackiesBabyy]

Whoops, I got that almost entirely wrong.

Clonidine binds to the a2a adrenergic receptor, which is used by your body to "sense" the levels of norepinephrine/adrenaline. So when you take a dose your body then thinks "whoa man I'm producing wayy too much noradrenaline" and hence the natural release of NE falls.

The end effect is pretty similar to an almost complete blockade of the effects of your body's natural NE/Adrenaline release.

The problem however is that clonidine etc, in long term therapy,are liable to cause rebound effects like absurdly high blood pressures when therapy is discontinues.

I don't think ephedrine would really benefit from anything more than a very small dose of clonidine - it's got too much intrinisc activity at the adrenergic receptors anyway. (Not only does it increase release of NE/DA it also mimics the effects of adrenaline and norepinephrine)

Ah, that makes a lot more sense. I knew my idea probably wouldn't work, I just find pharmacology fascinating If it worked someone most likely would have done it by now.

 

[raybeez]

a2a agonists (clonidine, guanfacine) are FDA-approved for combined use with stimulants in the treatment of ADHD. Not only to counteract side effects, but because they potentiate the effects of stimulants on learning and attention.

 

[xvaltan]

What about clonidine's proposed Imidazoline receptor agonist mechanism? Is there a possibility that both of the mechanisms are correct for it?

 

[endotropic]

Clonidine loses its hypotensive effect without functional alpha2a receptors, so the imidazoline agonism probably only plays a minor role there. I don't see any way imidazoline agonism could cause a decrease in NE release or boost in Ephedrine's recreational potential.

 

[xvaltan]

Clonidine loses its hypotensive effect without functional alpha2a receptors, so the imidazoline agonism probably only plays a minor role there. I don't see any way imidazoline agonism could cause a decrease in NE release or boost in Ephedrine's recreational potential.

Ah, thanks. Clears that up for me a bit. Interesting to know.

 

[m060mm]

Not only to counteract side effects, but because they potentiate the effects of stimulants on learning and attention.

Can I get a citation for that? Or could anyone chime in on the mechanism by which this could occur?

I ask because Sekio's explanation is my general understanding of clonidine.

Spoiler: Sekio's Explanation

Clonidine binds to the a2a adrenergic receptor, which is used by your body to "sense" the levels of norepinephrine/adrenaline. So when you take a dose your body then thinks "whoa man I'm producing wayy too much noradrenaline" and hence the natural release of NE falls.

The end effect is pretty similar to an almost complete blockade of the effects of your body's natural NE/Adrenaline release.

If that's the case, and it's agreed that therapeutic doses of amphetamines have a substantial effect on NE, how is clonidine supportive?

 

[sekio]

Because not all effects of amphetamine/ephedrine use are mediated by adrenaline/norepinehrine release.

 

[JackiesBabyy]

Can I get a citation for that? Or could anyone chime in on the mechanism by which this could occur?

I ask because Sekio's explanation is my general understanding of clonidine.


If that's the case, and it's agreed that therapeutic doses of amphetamines have a substantial effect on NE, how is clonidine supportive?

People with ADHD take amphetamines for dopamine, NE doesn't do shit for ADHD as you can see by the placebo NRI they give ADHD people who can't have controlled substances, Strattera.

 

[endotropic]

People with ADHD take amphetamines for dopamine, NE doesn't do shit for ADHD as you can see by the placebo NRI they give ADHD people who can't have controlled substances, Strattera.

I don't have the reference for this on hand, but I was under the impression that Adderall contains 25% levoamphetamine because levo releases more NE than dextro, and 100% dextroamphetamine is less effective for ADHD. I think the key is the balance between the two, not pure dopamine or NE releasing.

 

[negrogesic]

People with ADHD take amphetamines for dopamine, NE doesn't do shit for ADHD as you can see by the placebo NRI they give ADHD people who can't have controlled substances, Strattera.

This is a misconception. A casual glance of the binding values for D-amphetamine would suggest that D-AMP's most 'potent' action is on NE (note; this is purposefully simplistic illustration).

While I am not particularly impressed by this study, the basic principles are sound and may be relevant to this discussion:

http://onlinelibrary.wiley.com/doi/10.1111/j.1369-1600.2008.00138.x/full

 

[JackiesBabyy]

Be that as it may, for ADHD symptom control(I have ADHD and have tried all of these), desoxyn (equal to d-amp with more serotonin and less NE) > 4-FA (About 4x weaker as d-amp's NE release, but 2x weaker dopamine release and slightly less 5-HT release than meth, and while it's a lot weaker as a DA releaser I'm also taking a much higher dose of this than I would anything else) > D-amp (Twice as much NE as meth with 30% less dopamine and 2.5x weaker 5-HT release) > Adderall (can't find values for L-amp exactly but same thing more NE less dopamine less 5-HT).

Edit: Source for the numbers http://en.wikipedia.org/wiki/Releasing_agent