Misc mulungu toxicity?

[deruyityn]

http://www.scielo.br/scielo.php?pid=S0102-695X2011005000024&script=sci_arttext

Was reading that article and it says it might cause cancer at some doses if im reading it right? but gives no indication if a normal active dose would be toxic.

Anyone can demystify it a bit? didnt know what it was on about too much with all the science jargon.

I am looking for an anxiolytic for semi regular use (once or twice a week) so this would be no good if it is thought to be toxic.

Im also freaked out by its relation to poisons which is why ive not gone ahead and tried it yet.

 

[sekio]

This paper talks about mulungu being toxic... to onions.

It's a data point but it's nothing I'd lose sleep over.

 

[MagickalKat777]

Yeah I kind of laughed when I read that paper.

I've tried mulungu and I honestly didn't notice anything from the extract, if anything it actually made me more anxious but I'm not a good person to go by because of my pre-existing benzo tolerance.

 

[deruyityn]

This paper talks about mulungu being toxic... to onions.

It's a data point but it's nothing I'd lose sleep over.

Sure but doesnt it indicate it might well be toxic for humans. Ie now that they showed its toxic in one organic thing then it is more likely it will be toxic in another? As I said since Id be looking to use it on a semi regular basis I dont want to bet my health on only vague data. Does its fairly long history of use tell us anyhting about its longer term toxicity, ie would they likely have found a link between cancer and such and the substance or they might just not have made a connection?

Also regarding its relation to curare does that mean it could also cause paralytic death if at the wrong dose or Im guessing since its been used for such a long time without documented incident then that isnt likely?

Another concern I have is maybe there have been incidents but they arent reported since the rainforest is such a no man's land and theres even tribes they havent communicated with yet.

 

[sekio]

Sure but doesnt it indicate it might well be toxic for humans. Ie now that they showed its toxic in one organic thing then it is more likely it will be toxic in another?

How closely related are you to an onion or garlic plant?

The paper discusses some hypotheses about this, one of them is the notion that the genotoxic compounds may not be made w/o metabolism, and metabolic enzymes differ between different species, so there is no guarantee that it will have mammalian toxicity too. There is also the possibility that other repair mechanisms / elimination of the drug from the body will compete with any supposed genotoxicity.

Another bit of food for thought: harmine, the MAOI from ayahuasca, is a DNA intercalator and can cause weird cell cycle stuff, but it was also recently discovered it helps certain cells (like pancreatic beta cells) regenerate despite the fact. Also, people use ayahuasca (and drink coffee) and don't seem to get cancer immediaqtely afterwards, so there's that.

Also regarding its relation to curare does that mean it could also cause paralytic death if at the wrong dose

The alkaloids from mulungu and related plants are actually much closer to the papaverine type alkaloids from opium than anything from curare. Of course that says nothing about the actual toxic limit, but the evidence is there that it is used by some people on a regular or semi regular basis.

 

[deruyityn]

The alkaloids from mulungu and related plants are actually much closer to the papaverine type alkaloids from opium than anything from curare. Of course that says nothing about the actual toxic limit, but the evidence is there that it is used by some people on a regular or semi regular basis.

Interesting..what is your rationale for saying that? Mulungu has the same mechanism of action via the nacr receptors as curare...so how is it not similar to that?

Regarding the acute toxicity http://cdn.intechopen.com/pdfs-wm/18347.pdf that looks pretty good doesnt it. 5 times the ld50 of diazepam. but acute doesnt indicate safety vs chronic use does it. well maybe it points in the direction it is not going to be that bad for you but doesnt tell you what it will do over time right?

 

[sekio]

Interesting..what is your rationale for saying that? Mulungu has the same mechanism of action via the nacr receptors as curare...so how is it not similar to that?

People don't observe paralytic effects from dosing mice with mulungu extract for one. Secondly just because the alkaloids have affinity for nAChR it doesn't make them the primary target (lots of drugs hit nAChR ... DXM, nicotine, ibogaine, etc). Thirdly the structures of curare alkaloids are different from the mulungu alks.

Regarding the acute toxicity http://cdn.intechopen.com/pdfs-wm/18347.pdf that looks pretty good doesnt it. 5 times the ld50 of diazepam. but acute doesnt indicate safety vs chronic use does it. well maybe it points in the direction it is not going to be that bad for you but doesnt tell you what it will do over time right?

Mulungu has a traditional use as a medicine, somehow I suspect severe effects of chronic exposure would have been apparent with a few hundred years of usage.

 

[deruyityn]

People don't observe paralytic effects from dosing mice with mulungu extract for one. Secondly just because the alkaloids have affinity for nAChR it doesn't make them the primary target (lots of drugs hit nAChR ... DXM, nicotine, ibogaine, etc). Thirdly the structures of curare alkaloids are different from the mulungu alks.



Mulungu has a traditional use as a medicine, somehow I suspect severe effects of chronic exposure would have been apparent with a few hundred years of usage.

Ok, thanks for the clarification

 

[deruyityn]

What about what this guy says in this post:

http://www.bluelight.org/vb/threads/356351-Anxiolytic-Effect-of-Erythrina-mulungu-extract?p=6101842&viewfull=1#post6101842

I looked at the pics and indeed the molecules look exactly the same in shape

 

[sekio]

They have a similar tetracyclic structure, but erythravine is aromatic where erythroidine is a lactone.. that is a pretty major chemical change in therms of what binds where. There's also different positioning of double bonds and the alcohol group is masked with a methyl ether in the case of the latter, similar to the difference between molecules like codeine (active as narcotic) vs thebaine or codeine methyl ether (not narcotics but rather convulsants).

There's also the standard "dose makes the poison" type stuff to consider, the fate of this stuff in vivo, and relative levels of alkaloids from Mulungu.

 

[deruyityn]

Is there any practical safeguard against paralysis if I still have that paranoia on my mind?

Having a sitter ready to give cpr is the logical choice but unfortunately Ive been living as a hermit for a long time and have no social group to speak of let alone who could act as a sitter. Articifical ventilation doesnt seem to be a realistic option.

The only other other thing Ive thought of is dosing then just 'hanging around' outside a hospital

One could say if your that afraid don't take it, but the potential beenfits sound like it could be a boon to one's life (non addictive benzo could be extremely useful in many situations) if it turns out to be tolerated ok by the body. As you can see by my list of worreis I could really put a good anxiolytic to good use .

 

[sekio]

Mulungu is not a paralytic agent. Don't worry about such things.

 

[deruyityn]

Are there any other examples of otherwise toxic or lethal drugs that have related compounds or themselves which are used safely by humans?

Nicotine I was thinking was one I guess.

 

[sekio]

Codeine is a narcotic, thebaine is a non-narcotic convulsant.
Dopamine is a neurotransmitter needed for life, 6-hydroxydopamine will destroy every dopaminergic cell it touches.
Kratom alkaloids are related to reserpine, a neurotransmitter depleting compound that can cause extreme fatigue and depression.
Steroids like testosterone are relatives of the toxic cardiac glycosides found in poison dart frogs, nightshade, and foxglove.
LSD is a well-tolerated psychedelic agent, other ergot alkaloids can cause gangrene and other nastiness.
Pseudoephedrine is a decongestant that almost anyone can take 100mg of and feel nothing, methamphetamine at 100mg would give an average person a heart attack...

 

[deruyityn]

I was reading that some tetrahydroisoquinoline's may lead to parkinson's would that also apply to mulungu?

 

[deruyityn]

Thoughts mr sekio? I was reading that some thqs do and some don't so is it just russian roullette which may or may not lead to parkinsons?

 

[sekio]

Tetrahydroisoquinolines are a pretty big class of chemicals. Shulgin actually spent a lot of time looking at them and published a book on 'em after he did TiHKAL and PiHKAL.

I was reading that some thqs do and some don't so is it just russian roullette which may or may not lead to parkinsons?

It's not "russian roulette", these chemicals have known and defined effects and not every plant will contain every THQ in them. Some THIQs are produced naturally in the brain as minor products of dopamine breakdown. Some THIQs are neurotoxic and some are neuroprotective[ref] (generalized classes of structure aren't a good predictor of activity, e.g. technically speaking even morphine is a tetrahydroisoquinoline) and some can be either helpful or toxic depending on dose levels. And more importantly just because a plant contains a detectable amount of toxic component in some parts, doesn't mean it has enough to be toxic... even common white button mushrooms contain traces of toxic mycotoxins.

Consider the following: para-methoxyamphetamine (PMA, toxic MDMA analog), buproprion (Wellbutrin, antidepressant), 25I-NBOMe (psychedelic) and methamphetamine (neurotoxic stimulant) are all phenethylamines... does that then mean they all are randomly interchangable in terms of effects? All evidence points to 'no'.

If you are not comfortable with using a substance which has only been used in a traditional context, don't feel pressured to do so.

 

[deruyityn]

I just read this interesting paper. It's nice to see a relatively up to date study (2012) on the matter. Translated from porteguese so I guess an in house brazilian study:

http://translate.google.co.uk/trans...22012000200014&script=sci_arttext&prev=search

Could someone more chemistry minded help expand on what is being said. From what I read no acute toxicity or genotoxicity however genotoxicity from chronic use should not be ruled out. Given the data does this imply any greater risk than other common herbs/intoxicants?

When talking of inflorescence they mean the bark, right which is the active compenent which is used in common preparation?

 

[Mycophile]

If I get a chance I'm going to order this stuff and try it.

Even if there does happen to be any toxicity, which Sekio keeps saying there isn't, I doubt it would be a problem to try a couple times.

Deruyityn, I think you worry a bit too much about this kind of stuff, and that's coming from a guy who worries a lot.

I guess I am maybe a bit more comfortable experimenting with lightly less known drugs than you.

That could be a good or bad thing.

 

[deruyityn]

Oh for fucks sake. Just when i was almost onboard to try this one I started reading up more about genotoxicity and genotoxic = cancer!

I know it was discussed a little above regarding the onions but doesnt the ltest link I posted add tot he evidence of its possible genotoxicity?

Isnt the concluding paragraph of my latest link saying that the inflorescence (root) causes mutogenic effects regardless of dose? Ie it is genotoxic at any dose?

Hope this can be expanded on by someone more knowledgable as to the relative risk of semi chronic use. Doesnt look good from my reading.

People say 'just don't take it' but Im still gagging for some kind of anxiolytic due to my hypochondriac nature so it doesnt just solve the problem.