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ThirdEyeGrind
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Discussion Starter · #3 ·
I seem to remember that opiates are potentiated by MAOIs, such that you need a lower dose for equal effects. Possibly true for kratom, I have no idea. Start with a much lower dose than normal.
But the thing is, at low doses of Kratom it has a stimulating effect. And stimulants are a no no with maoi's, except for ....i can't remember the name of it. Its the one that doesn't really have a stimulant effect at all, it just keeps you awake (supposedly), and costs waaay too much for what its worth.
 

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ThirdEyeGrind
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Discussion Starter · #4 ·
I was hoping Rocknroll714 would enlighten me with his supreme knowledge. If not, then has anyone tried this combination before? Also, I've only been taking the nardil 15mg twice a day for only 2 days now so I don't even know if I've been taking the Nardil long enough to have a dangerous effect (if this combination does infact cause dangerous effects).
 

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Equilibrian Epicurius
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Wikipedia said:
Although structurally related to yohimbine and other tryptamines, its pharmacology is quite different, acting primarily as a mu-opioid receptor agonist. It also shares some adrenergic receptor activity similar to that of yohimbine.
Opioids that act solely on the mu-opioid receptors I believe are safe when combined with MAOIs, although as euphoria stated may be potentiated. I wonder what the adrenergic activity means though, maybe that Kratom could have cardiovascular effects? I'm not sure if the increased epinephrine and norepinephrine from Nardil combined with that could be dangerous.
 

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ThirdEyeGrind
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Discussion Starter · #6 ·
Opioids that act solely on the mu-opioid receptors I believe are safe when combined with MAOIs, although as euphoria stated may be potentiated. I wonder what the adrenergic activity means though, maybe that Kratom could have cardiovascular effects? I'm not sure if the increased epinepherine and norepinephrine from Nardil combined with that could be dangerous.
Ok, so this is a like a 50/50 chance of not knowing what will happen? I know for fact when I was on 90mg Nardil I could take Opiates and have absolutely no problem. Infact, the hospital even gave me shots of painkillers at the hospital once when I had a hypertensive reaction to Ephedra. Wait, so are you saying it should/might be safe? What do you mean by mu-opioid receptors? I'm sorry, I'm not as educated as you and others on this forum.
 

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Kratom being an opioid (mu-receptor-agonist) is not a problem, just a dose reduction might be necessary, but Kratom having stimulant properties could cause some troubles.
 

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ThirdEyeGrind
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Discussion Starter · #8 ·
Thanks for the info people. I just wish there was some actual evidence online that there would be no problems. Its the whole stimulant property of Kratom thats got me worried to take it. Again thankyou. And any other information would be helpful aswell.
 

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Equilibrian Epicurius
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I'm not well educated on the subject of adrenergic receptors so I'm rather confused here as well. Hopefully one of the pharmacology experts on this site (euphoria, Rocknroll714, Medline, or anyone else who is well-versed in this stuff) could enlighten me on this subject:

According to Wikipedia, norepinephrine and epinephrine are α1, α2, β1, β2, and β3 adrenergic receptor agonists. If this is the case, then why don't MAOIs increase blood pressure and heart rate since they boost the levels of both these catecholamines? If yohimbine is an α2 antagonist, then what could cause the hypertension and tachycardia side effects? Unopposed action at the α1 receptor seems like the only possible explanation.

Some stimulating drugs can be perfectly safe when used in conjunction with an MAOI, it just depends on their pharmacology. Some people have reported mild stimulating effects from both gabapentin and to a larger extent pregabalin, but since these are only calcium channel blockers they don't interfere with MAOIs besides temporarily reducing noradrenaline release.

Ok, so this is a like a 50/50 chance of not knowing what will happen? I know for fact when I was on 90mg Nardil I could take Opiates and have absolutely no problem. Infact, the hospital even gave me shots of painkillers at the hospital once when I had a hypertensive reaction to Ephedra. Wait, so are you saying it should/might be safe? What do you mean by mu-opioid receptors? I'm sorry, I'm not as educated as you and others on this forum.
I would refrain from trying it until more information about it's pharmacology is revealed, it's quite difficult to determine how this combination could effect you without knowing more about it's adrenergic activity. If Kratom does in fact share the same adverse cardiovascular effects of yohimbine then I think it could definitely be dangerous, but then again I don't know very much about adrenergic receptors.

The mu-opioid receptor is the primary opioid receptor that most opiates act on. Since MAOIs alone have absolutely no effect on opioid receptors, opiates than bind only to these receptors are safe to use while on an MAOI.
 

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According to Wikipedia, norepinephrine and epinephrine are α1, α2, β1, β2, and β3 adrenergic receptor agonists. If this is the case, then why don't MAOIs increase blood pressure and heart rate since they boost the levels of both these catecholamines? If yohimbine is an α2 antagonist, then what could cause the hypertension and tachycardia side effects? Unopposed action at the α1 receptor seems like the only possible explanation.
MAOIs can produce low blood pressure and heart rate due to increased octopamine:

wikipedia said:
Chronic use of MAOIs may provide some antidepressant effects that are thought to be mediated by metabolism of tyramine to octopamine, a reaction catalyzed by phenyl-N-methyl transferase that normally converts dopamine to norepinephrine. Octopamine may then act as a "false transmitter" in that it is stored and released like the endogenous transmitter norepinephrine. However, it is a poor agonist of postsynaptic adrenoceptors while retaining agonist activity at presynaptic autoreceptors. This action reduces adrenergic transmission by diminishing postsynaptic receptor activation and by a presynaptic autoinhibitory effect. Finally, octopamine may serve as an agonist at a novel "trace amine" receptor expressed at low levels throughout the brain.
They also boost epinephrine, norepinephrine, PEA and others, but this is usually offset by octopamine. However, if you take adrenergic precursors or adrenergic drugs, the octopamine effect will likely be overpowered and you'll be heading for hypertension. I would expect alpha-2 antagonists (e.g. yohimbine) to be massively potentiated by MAOIs, as alpha-2 is an autoreceptor whose blockade increases norephinephrine. I believe direct adrenergic agonists on receptors other than alpha-2 would have a more linear additive effect rather than synergistic potentiation, so might not be so dangerous (still not recommended!).

I would refrain from trying it until more information about it's pharmacology is revealed, it's quite difficult to determine how this combination could effect you without knowing more about it's adrenergic activity. If Kratom does in fact share the same adverse cardiovascular effects of yohimbine then I think it could definitely be dangerous, but then again I don't know very much about adrenergic receptors.
Yeah, this is good advice. So far I haven't seen any conclusive evidence for Kratom's non-opioid mechanisms of action, so it's best left alone unless you have a syringe full of carvedilol or clonidine on hand.
 

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ThirdEyeGrind
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Discussion Starter · #11 ·
This is gonna make my head explode. There's no sources at all online that say if this is a ok or not ok combination. I really do appreciate all your guys information. How the hell did you get so smart so young? Well, I dabbed my finger into some Kratom (not even a grams worth), and have had no bad reaction after eating it. Its been about a half an hour. I don't even think its enough to notice any kind of reaction good or bad. Does anyone have any other info on this subject? If not then I'll just shut up about it. Its just driving me nuts cause I ordered this stuff and it came a frickin day after I started Nardil. And I didn't plan on starting Nardil again either, my pdoc and me just sorta agreed to it.
 

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ThirdEyeGrind
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Discussion Starter · #12 ·
I've had maybe close to 1 gram and am feeling sorta uppedy but it could very well be the placebo effect. No headaches thank god. Damn I'm dumb for doing this. Atleast if I have no problems there will be a single report of this combination on the interweb. Me playing the guinnee pig.....like an idiot.
 

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Equilibrian Epicurius
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Measure your heart rate when not on Kratom, then check it after you've consumed some and see if it rises. Also, if you don't already have an automatic blood pressure cuff it would be a good idea to purchase one... that way you can consistently monitor if you're having a dangerous cardiovascular event.
 

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ThirdEyeGrind
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Discussion Starter · #14 ·
Ok so today I ingested about 7 grams (not all at once) and have had no negative effects whatsoever. I also ordered this Kratom online and can tell that its really really weak compared to what you buy in head shops. Anyway, I'd say its safe to say its absolutely safe to combine Nardil with Kratom (atleast in my case). Again thanks for your help (Euphoria/IllusionalFate/Medline/rocknroll714). And to IllusionalFate, I haven't noticed any difference in my blood pressure compared to being on and off Kratom. This is just me though.
 

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If yohimbine is an α2 antagonist, then what could cause the hypertension and tachycardia side effects? Unopposed action at the α1 receptor seems like the only possible explanation.
This is backwards. α2 receptor activation is antihypertensive (clonidine) and can induce states resembling physiologic sleep (such as with dexmedetomidine). It decreases the release of norepinephrine among other things. So yohimbine increases norepinephrine levels by antagonizing α2.
 
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